Phase 2 Single-Arm Rectal Cancer Brachytherapy for Patients With Low-Lying Residual Adenocarcinoma After Total Neoadjuvant Therapy to Improve Organ Preservation Rates
Rectal cancer patients who do not achieve a complete response to standard of care chemotherapy and radiation often require surgical resection as part of curative intent therapy. This study will evaluate whether additional focal radiation delivered internally (rectal brachytherapy) can provide complete responses and thus spare the requirement for surgery. The main questions are whether: 1) rectal brachytherapy is safe in this clinical treatment paradigm and if 2) rectal brachytherapy improves organ preservation (no need for surgery). The trial involves an additional MRI pelvis and sigmoidoscopy with marker placement to define high-risk residual disease for radiation planning. Subsequently, 3 outpatient brachytherapy treatments are given on a weekly basis. If a patient achieves a complete response to brachytherapy, standard of care non-operative surveillance visits are conducted with study visits aligned during the first two years following brachytherapy.
• 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