Inclusion Criteria:

- Patients must have histologically proven adenocarcinoma of the rectum with no
evidence of distant metastases.

- The tumor must be clinically Stage II (T3-4 N0) or III (T1-4 N1-2).

- Patients must have no evidence of distant metastases including liver metastases,
peritoneal seeding, or inguinal lymphadenopathy.

- Patients who completed or are actively enrolled in the CONTRE study and patients
undergoing treatment for rectal cancer following the TNT (Total Neoadjuvant
Treatment) format (see below) for whom sufficient tissue is available for the
required research analyses may be enrolled in this study retroactively.

- For those who have not yet received treatment for rectal adenocarcinoma, these
patients must not have received prior chemotherapy or pelvic radiation for rectal
cancer, or prior pelvic radiation for any other malignancy that would prevent the
patient from receiving the required radiation treatments for this study.

- Patients must not have an active concurrent invasive malignancy other than
non-melanoma skin cancers. Patients with malignancies diagnosed within 5 years prior
to randomization which have been effectively treated and are deemed to be at low risk
for recurrence are eligible.

- Patients must be > 18 years of age, ECOG (performance status) 0-1.

- ANC (absolute neutrophil count) >1,500/µl, platelets >100,000/µl, total bilirubin
<2.0 mg/dl or direct bilirubin <1.0 mg/dl, alkaline phosphatase <3xULN, ALT <3xULN,
creatinine <1.5xULN.

- Signed informed consent; able to comply with study and/or follow- up procedures

- Peripheral neuropathy < grade 1.

- The intention of the treating physicians is to administer Total Neoadjuvant Treatment
as per the suggested treatment guidelines in section 4 and section 5 or as per
standard institutional policies.

Exclusion Criteria:

- Evidence of metastatic disease.

- Rectal cancers other than adenocarcinoma, i.e., sarcoma, lymphoma, carcinoid,
squamous cell carcinoma, cloacogenic carcinoma, etc.

- Pregnancy or lactation at the time of proposed randomization. Eligible patients of
reproductive potential (both sexes) must agree to use adequate contraception.

- Synchronous invasive colon cancer.

- Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would
preclude the patient from receiving any chemotherapy treatment option or would
prevent required follow-up.

- Patients with active inflammatory bowel disease, abdominal fistula, gastrointestinal
perforation, or intra-abdominal abscess within 6 months prior to Day 0 or other
serious medical illness which might limit the ability of the patient to receive
protocol therapy.

- Known hypersensitivity to 5-fluorouracil or oxaliplatin

- Psychiatric or addictive disorders or other conditions that, in the opinion of the
investigator, would preclude the patient from meeting the study requirements.

- Insufficient tumor tissue available for the required genomic analyses and patient
unable or unwilling to undergo repeat examination and biopsies.