Tumor Cell and DNA Detection in the Blood, Urine and Bone Marrow of Patients With Solid Cancers

Background:

Patients with resectable solid primary cancers and even limited number of metastases are
potentially curable. However, most patients develop recurrences despite surgery. Circulating
and disseminated tumor cell (CTC/DTC) and circulating cell-free (cf) DNA isolation from the
blood, urine and bone marrow will increase understanding of cancer spread and advance
knowledge to develop individualized therapies.

Hypothesis and Rationale:

CTCs/DTCs and cfDNA isolated from the blood, urine and bone marrow during cancer surgeries
undergo pheno- and/or genotype changes. CTCs/DTCs have potential for dissemination and tumor
growth in vivo. Investigating the biology of liquid biomarkers in the blood, urine and bone
marrow will significantly increase understanding of cancer biology.

Specific Aims:

CTCs/DTCs and cfDNA isolated from cancer patients will be characterized for genetic
alterations and expression of key signaling/proliferation biomarkers and grow in vivo in nude
mice.

Study Design:

100 patients undergoing solid cancer surgeries will be recruited for perioperative
CTC/DTC/cfDNA isolation from the blood, urine and bone marrow with innovative techniques. In
addition, 10 patients undergoing similar surgeries for benign disease will also be included
as controls. CTCs/DTCs, cfDNA and cancer tissue pheno- and/or genotype analysis will be
performed with different innovative techniques. Furthermore, CTCs/DTCs will be enriched,
cultured and characterized. Tumor growth potential will be studied in nude mice.

Relevance:

This translational cancer trial addresses fundamental aspects of cancer disease being the
cause of death in 1 out of 4 persons in the US. Innovative CTCs/DTCs characterization can
shed light on the tumor biology, and identify therapy targets. Results of this study can be
fundamentally important to understanding cancer spread and development of personalized
therapies.

Inclusion Criteria:

- Subjects older than 18 years.

- Subjects of all genders and ethnicities.

- Subjects with the diagnosis of a solid cancer (n=100) of all stages will be included
(lung, esophageal, stomach, bile duct/pancreas, colorectal, melanoma, sarcoma).

- Ten patients with no present suspicion and no previous history of any cancer (except
basal cell cancer of the skin) that undergo surgeries for other benign indications
will serve as controls (n=10).

- In patients undergoing surgery for cancer the histopathology should preferably be
pathologically proven by a previous or novel biopsy. Yet, patients with a high cancer
suspicion by radiology and clinical picture that undergo cancer surgery will not be
excluded. No additional biopsies, testing or interventions will be performed for the
purpose of this study if the medical treatment will not require it.

- Subjects must be capable of giving informed consent.

Exclusion Criteria:

- Pregnant women.

- Subjects with the concurrent diagnosis of an active secondary (synchronous) malignancy
besides basal cell carcinoma of the skin will be excluded, if there is evidence of
disease burden or if the patient is currently being treated with chemotherapy.

- Subjects with a hemoglobin of <8g/dl in the morning of the procedure will be excluded.

- In subjects who require intraoperative transfusions of >4 units of red packed blood
cells (RPBCs), no further blood will be drawn for CTC/DTC/cfDNA analysis during
surgery or on postoperative day 1.

- In patients with coagulation disorders that could lead to significant bleeding (such
as hemophilia, significant thrombocytopenia) requiring prophylactic administration of
coagulative products, no bone marrow aspiration will be performed.