The purpose of the study is to learn more about how the body responds to standard treatment (chemoradiation and chemotherapy). The study will use the results of testing down on participants' blook, tissue, and scans to learn more about how people with rectal cancer respond to chemoradiation and chemotherapy treatment and if it is useful for predicting whether a person's cancer get better, gets worse, or stats the same after treatment.

Inclusion Criteria:

• 18 years of age or older on day of signing informed consent.

• Have a histologically confirmed diagnosis of invasive adenocarcinoma of the rectum with no known mismatch repair deficiency or Her2 amplification.

• Eligible for and plan to initiate standard-of-care therapy with any of the following regimens:

  • Induction fluoropyrimidine (capecitabine [preferred] or 5-FU) based chemoradiation
  • With plan for consolidative CAPEOX, FOLFOX, or FOLIRINOX

• Woman with childbearing potential who are negative for pregnancy test (urine or blood) and who agree to use an effective contraceptive method. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. Reliable contraception should be used from the time of screening and must be continued throughout the duration of treatment as per standard of care.

Exclusion Criteria:

• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
• Patients with prior external beam radiation therapy to the pelvis or brachytherapy seed implantation of the prostate.
• Patients who are pregnant or breastfeeding.
• Men or women not using effective contraception.
• Patients with a contraindication to MR imaging.
• Patients on blood thinners prohibiting endoluminal tumor biopsies.

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.