Rectal Cancer, Adenocarcinoma
Conditions
Keywords
Rectal cancer, Organ preservation, High-dose-rate brachytherapy, Endorectal brachytherapy, 3D-printed template, Tungsten alloy shielding
Brief summary
This prospective, single-center, single-arm phase II study will evaluate the efficacy, safety, and technical feasibility of an organ-preserving radiotherapy strategy for patients with localized rectal adenocarcinoma who are medically inoperable, decline radical surgery, or are considered technically unresectable without distant metastases. Participants will receive pelvic external beam radiotherapy followed by high-dose-rate (HDR) endorectal brachytherapy. Concurrent capecitabine may be given during external beam radiotherapy to participants who are considered able to tolerate chemotherapy. During HDR brachytherapy, all participants will be treated using a patient-specific 3D-printed guide template and individualized tungsten-alloy local shielding. The guide template is designed to improve applicator positioning and treatment reproducibility, while the local shielding is intended to reduce radiation exposure to non-target rectal wall. The study will enroll 50 participants. The primary objectives are to evaluate the 12-month clinical complete response rate and the technical completion rate of the HDR brachytherapy platform. Secondary assessments include organ preservation, local regrowth, survival outcomes, treatment-related toxicity, quality of life, and anorectal function.
Detailed description
This investigator-initiated study is a prospective, open-label, single-arm phase II trial evaluating a definitive non-operative treatment strategy for localized rectal cancer. Eligible participants will have histologically confirmed rectal adenocarcinoma without distant metastases and will be considered medically unsuitable for radical surgery, decline radical surgery after appropriate counseling, or be considered technically unresectable by multidisciplinary assessment. Following baseline evaluation and multidisciplinary review, participants will receive pelvic external beam radiotherapy. The planned dose to the pelvic planning target volume is 45 Gy in 25 fractions. Radiologically positive or highly suspicious lymph nodes will receive a simultaneous integrated boost to 55 Gy in 25 fractions, with escalation to 58-58.25 Gy in 25 fractions permitted when considered dosimetrically safe. Concurrent capecitabine at 825 mg/m² twice daily on radiotherapy days may be administered to participants who are considered able to tolerate chemotherapy; concurrent chemotherapy is not mandatory in this study. Participants will undergo reassessment approximately 4-6 weeks after completion of external beam radiotherapy before proceeding to HDR endorectal brachytherapy. The planned HDR boost is 6 Gy per fraction for 3 fractions using an iridium-192 source, with fractions generally separated by 5-7 days. During all HDR fractions, a patient-specific 3D-printed guide template will be used for applicator positioning, fixation, and reproducibility. Individualized flexible tungsten-alloy shielding, typically approximately 3 mm thick, will be positioned within a predefined channel in the template before treatment. The shielding configuration will be individualized according to tumor distribution and the location of non-target rectal wall requiring protection. Because the shielding material may produce substantial computed tomography artifacts, treatment planning will be performed before placement of the tungsten-alloy shielding, followed by verification of shielding direction, depth, and fixation before irradiation. Tumor response will be assessed using a combination of digital rectal examination, endoscopy, and pelvic magnetic resonance imaging. Participants achieving a clinical complete response will enter a structured watch-and-wait follow-up program. Participants with residual disease, local regrowth, or progression will undergo multidisciplinary reassessment for individualized salvage treatment when appropriate. In addition to clinical response and organ-preservation outcomes, the study will prospectively evaluate treatment-related toxicity and the technical performance of the individualized brachytherapy platform, including treatment completion, geometric reproducibility, shielding implementation, and dosimetric parameters.
Interventions
RADIATIONHigh-Dose-Rate Endorectal Brachytherapy
High-dose-rate (HDR) endorectal brachytherapy will be delivered as a local dose-intensification component of the organ-preserving treatment strategy for rectal cancer. Brachytherapy will be performed using image-guided, patient-specific treatment planning to optimize target coverage while limiting radiation exposure to adjacent organs at risk. Treatment technique, applicator placement, dose prescription, and fractionation will be performed according to the study protocol.
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-80 years. 2. Histologically confirmed rectal adenocarcinoma. 3. Clinical stage cT2-4, any N, M0. 4. Patients who are elderly or frail, medically unsuitable for radical surgery, refuse radical surgery, or are considered by a multidisciplinary team (MDT) to have disease for which safe R0 resection is technically difficult. 5. Considered by the MDT and investigators to be suitable for a definitive non-operative treatment strategy. 6. ECOG performance status 0-2; patients with ECOG performance status 3 may be eligible if considered by the MDT to be able to tolerate the study treatment. 7. Estimated life expectancy of at least 6 months. 8. Considered suitable for pelvic external beam radiotherapy and HDR endorectal brachytherapy. 9. Tumor location, endorectal access, and local anatomy suitable for HDR brachytherapy using the individualized 3D-printed guide template. 10. Adequate hematologic, hepatic, and renal function for the planned treatment. 11. Ability to understand the study requirements and provide written informed consent.
Exclusion criteria
1. Distant metastatic disease or disease considered unsuitable for definitive local non-operative treatment. 2. Prior definitive pelvic radiotherapy. 3. Intestinal perforation, complete bowel obstruction, uncontrolled active bleeding, or severe active infection. 4. Anatomical or clinical conditions precluding HDR endorectal brachytherapy or use of the individualized guide template/local shielding platform. 5. Inflammatory bowel disease. 6. Severe uncontrolled cardiopulmonary disease, significant bone marrow suppression, or severe hepatic or renal dysfunction. 7. Pregnancy or breastfeeding. 8. Concurrent participation in another clinical trial that may interfere with evaluation of the study treatment or endpoints. 9. Any other condition considered by the investigator to make the patient unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 12-Month Clinical Complete Response Rate | From completion of study treatment through 12 months | Percentage of participants who maintain a clinical complete response (cCR) at 12 months after completion of study treatment, without local regrowth and without rectal cancer-related salvage resection. Clinical response will be assessed using a composite evaluation including digital rectal examination, endoscopy, and pelvic magnetic resonance imaging. |
| Technical Completion Rate of HDR Brachytherapy | Through completion of HDR brachytherapy, approximately 8-10 weeks after completion of external beam radiotherapy | Percentage of participants who complete all three planned high-dose-rate (HDR) endorectal brachytherapy fractions using the study-specific 3D-printed individualized guide template and tungsten alloy local shielding platform as required by the study protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Clinical Complete Response Rate | From completion of study treatment through 12 months | Percentage of participants who achieve a clinical complete response (cCR) after completion of study treatment. Clinical response will be assessed using a composite evaluation including digital rectal examination, endoscopy, and pelvic magnetic resonance imaging. |
| Near-Clinical Complete Response Rate | From completion of study treatment through 12 months | Percentage of participants classified as having a near-clinical complete response (near-cCR) after completion of study treatment based on composite assessment using digital rectal examination, endoscopy, and pelvic magnetic resonance imaging. |
| 12-Month Organ Preservation Rate | From completion of study treatment through 12 months | Percentage of participants who remain alive with the rectum in situ and without rectal cancer-related radical salvage resection at 12 months after completion of study treatment. |
| Local Regrowth Rate | From completion of study treatment through 24 months | Percentage of participants who develop local tumor regrowth after achieving a clinical complete response or near-clinical complete response during follow-up. Local regrowth will be assessed using digital rectal examination, endoscopy, pelvic magnetic resonance imaging, and other clinically indicated assessments. |
| Local Failure-Free Survival | from enrollment through 24 months | Time from completion of study treatment to the first occurrence of local treatment failure or death, whichever occurs first. |
| Progression-Free Survival | from enrollment through 24 months | Time from completion of study treatment to the first documented disease progression, local or distant recurrence, or death from any cause, whichever occurs first. |
| Overall Survival | from enrollment through 24 months | Time from completion of study treatment to death from any cause. |
| Stoma-Free Survival | from enrollment through 24 months | Time from completion of study treatment to permanent stoma creation or death from any cause, whichever occurs first. |
| Incidence of Acute Treatment-Related Adverse Events | From initiation of study treatment through 90 days after completion of study treatment | Percentage of participants experiencing acute treatment-related adverse events, with particular attention to grade 3 or higher gastrointestinal toxicity, bleeding, pain, ulceration, stenosis, and treatment-related functional impairment. Adverse events will be graded according to NCI-CTCAE version 5.0. |
| Incidence of Late Treatment-Related Adverse Events | From more than 90 days after completion of study treatment through 24 months | Percentage of participants experiencing late treatment-related adverse events, with particular attention to grade 3 or higher gastrointestinal toxicity, rectal bleeding, ulceration, stenosis, pain, and treatment-related functional impairment. Adverse events will be graded according to NCI-CTCAE version 5.0. |
Countries
China
Contacts
CONTACTYuanjie Cao, MD
PRINCIPAL_INVESTIGATORYuanjie Cao, MD
Tianjin Medical University Cancer Institute and Hospital
Outcome results
None listed