A prospective study for the assessment of recurrence risk in stage II colon cancer patients using ColoPrint.

Despite numerous clinical trials, the benefit of adjuvant chemotherapy for
stage II colon cancer patients is difficult to prove. Three-fourth of patients
is cured by surgery alone and therefore, less than 25% of patients would
benefit from additional chemotherapy. The identification of the sub-group of
patients that are more likely to suffer from a recurrent disease would allow
identifying those patients who should be treated after surgery. Current
pathological prediction factors, most prominent staging, are not sufficient to
identify *high risk* patients in either subgroup. For example, the finding
that patients with stage IIB have a worse prognosis than patients with stage
IIIA highlights the need to find better prognostic factors. Other clinical
parameters like grade, number of assessed lymph nodes or vascular invasion are
currently not used by all doctors in the same way. Additionally, the magnitude
of risk conferred by these characteristics cannot be reliably estimated from
available data.
Using microarray technology and tumor classification methods, a subset of genes
was identified that are predictive for the prognosis of recurrence of stage II
and III colon cancer (ColoPrint). In the training and validation set, the
prognostic profile was more powerful than ASCO recommendations for selecting
high risk stage II patients. Furthermore, mulitivariate analysis indicated that
a combination of classifier and selected clinical variables could even more
powerful and accurate in identifying high risk patients. A more detailed
comparison between prognostic profile and clinical parameters should be
addressed in this study.

1. Organization and controlled implementation of ColoPrint® for prognosis
prediction
2. In stage II patients, prospective comparison of risk assessment by ColoPrint
profile versus clinical parameters based on local protocol and ASCO high-risk
recommendations which account for the presence of at least one of the
following: T4, perforation/ obstruction, G3, and inadequate node sampling (less
than 12 nodes).
3.Establishment of proportion *good prognosis profile* and *poor prognosis
profile* in stage II and stage III colon cancer patients in various European
countries
4. In stage III patients, exploratory analysis of the efficiency of ColoPrint
in identifying low risk subgroups
5. Validation of the power of risk assessment

This study will address the logistic and quality assurance of using ColoPrint
in clinical practice. The entire procedure of collecting and sending tissue
samples, respective transfer of information, processing the tissue samples,
carrying out diagnostic activities and reporting to the attending clinician
must be set up at this stage (feasibility and implementation). In addition,
risk assessment results from the prognostic profile (ColoPrint) will be
compared to the risk assessment resulting from various clinical parameters
following ASCO criteria and independent investigator risk assessment. The aim
is to enroll maximal 600 stage II patients in order to compare the performance
of ColoPrint against the clinical risk assessment in estimating 3 year relapse
rate. The treatment of the patient is at the discretion of the physician.
Stage III patients will be analyzed on an exploratory basis. First 300 patients
will not receive the study results. Second 300 patients will receive the study
results.

After receipt of the results, the treatment of the patient is at the discretion
of the physician. Patients will spend time reading the patient information and
informed consent. The trial is not invasive. Patients will be asked permission
for further use of their tumor tissue and sharing of clinical information with
Agendia.