Phase 2 Single-Arm Rectal Cancer Brachytherapy for Patients With Low-Lying Residual Adenocarcinoma After Total Neoadjuvant Therapy to Improve Organ Preservation Rates

Prior treatment

• Pelvic radiotherapy given prior to rectal cancer external beam radiation.
• Prior colorectal surgery in which anastomotic site is at or near HDR brachytherapy target.
  • o Prior local excision is not an exclusion criterion.
• Concurrent administration of any cytotoxic chemotherapy, immunotherapy, or other any targeted oncologic agent that would impact rectal cancer is not allowed during study protocol.
• If rectal cancer has been treated outside of standard total neoadjuvant therapy per NCCN guidelines, patients are ineligible for the trial. This includes if patients received external beam chemoradiation dose with prescription \>56 Gy or short-course radiation to rectal mucosa prescription \>30 Gy.

Other illness

• History of ulcerative colitis or Crohn's disease.
• Uncontrolled intercurrent severe illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.

Age

• Life expectancy \<3 years per provider discretion.

Other

• Pregnant women.

• Provision to sign and date the consent form.
• Stated willingness to comply with all study procedures and be available for the duration of the study.
• Adults (18-100 years old)
• ECOG 0-3
• Patients with MMR-proficient low-mid rectal adenocarcinoma cT1-4 N0-2 M0 who underwent total neoadjuvant therapy who have not achieved complete response (i.e. incomplete or near-complete) in the rectal primary tumor such that surgical resection, if offered presently or in the future, would be an APR or low LAR per colorectal surgeon expert opinion and central review at University of Colorado rectal tumor board. Tumor restaging will be 4-16 weeks following completion of total neoadjuvant therapy, and no sooner than 8 weeks if patients received chemotherapy followed by chemoradiation/short course radiation.
• Residual rectal disease must have its craniocaudal extent \<4 cm with thickness \<1.2 cm. Tumor must have \<50% circumferential involvement. Residual disease must be above the dentate line and not involving the anal canal.
• In patients with original cN1-2 disease, restaging CT and MRI after total neoadjuvant therapy must demonstrate at least near-complete response of the pelvic lymph nodes per NCCN criteria as evaluated by central review at University of Colorado rectal tumor board.
• Interval of time between completion of TNT and initiation of rectal brachytherapy must be between 4-16 weeks.
• Patients must be recovered from total neoadjuvant therapy and must not have significant rectal incontinence at time of screening.
• Received conventionally fractionated external beam chemoradiation between 45-56 Gy or short-course external beam radiation prescription of 25 Gy to rectal mucosa, in addition to systemic chemotherapy before or after radiation per National Comprehensive Cancer Network (NCCN) guidelines.
• Women of child-bearing potential must have a negative urine or serum pregnancy test within 14 days of HDR treatment.
• Men and women of reproductive potential who are sexually active must agree to follow instructions of contraception for the duration of the study and 6 months post-rectal brachytherapy completion.
• CBC at the time of screening must have platelets\>50 10\^9/L, Hemoglobin\>8 g/dL and Absolute Neutrophil Count \> 500 10\^9/L