Ultra-fractionated Radiotherapy for Rectal Cancer

Inclusion Criteria:

1. At least 18 years of age. Both men and women and members of all races and ethnicgroups will be included.

2. Willing and able to provide written informed consent

3. Pathologic diagnosis of rectal adenocarcinoma

4. T3-4 and/or N+ disease per AJCC 8th edition

5. No prior treatment for rectal adenocarcinoma

6. Eastern Cooperative Group (ECOG) performance status of 0-2.

7. Laboratory values supporting acceptable organ and marrow function within 30 days ofeligibility confirmation. Defined as follows:

• WBC ≥ 3,000/mL;

• ANC WBC ≥ 1,000/mL;

• PLT ≥ 75,000/mL;

• T Bili ≤ 1.5 x upper limit of normal (ULN);

• AST/ALT ≤ 2.5 x ULN;

• Creatinine not above ULN, or creatinine clearance >50 mL/min/1.73 m^2 forparticipants with creatinine levels above institutional normal.

8. All men, as well as women of child-bearing potential must agree to use adequatecontraception (hormonal or barrier method of birth control; abstinence) startingwith the first dose of study therapy through 90 days after the last dose of studydrugs. Should a woman become pregnant or suspect she is pregnant while participatingin this study, she should inform her treating physician immediately.

A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy; or

• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., hashad menses at any time in the preceding 12 consecutive months).

Exclusion Criteria:

1. Distant nodal disease (retroperitoneal nodes) including inguinal nodes, or anymetastatic disease by CT.

2. Prior RT to the pelvis.

3. Uncontrolled comorbid illness or condition including congestive heart failure,unstable angina, cardiac arrhythmia, or psychiatric illness that would limitcompliance with the study requirements.

4. Psychiatric illness/social situations that would limit consenting and compliancewith study requirements.

5. Participants who are pregnant or nursing due to the potential for congenitalabnormalities and the potential of this regimen to harm nursing infants