This is a single-center, Phase II prospective pilot study designed to evaluate the feasibility, safety, and early clinical outcomes of high-dose-rate (HDR) endorectal brachytherapy delivered using the Maastro applicator in patients with histologically confirmed rectal cancer.
Rectal cancer is commonly treated with surgery, frequently combined with chemotherapy and/or external beam radiotherapy (EBRT) in locally advanced disease. While surgery provides effective local control, it may be associated with substantial morbidity, including the risk of a permanent stoma and functional impairment. These concerns are particularly relevant in older patients or those with significant comorbidities. Consequently, there is increasing interest in organ-preserving strategies for selected patients who achieve a favorable response after non-operative treatment, provided that rigorous surveillance is maintained.
Contact-type local radiation boost approaches, including contact X-ray brachytherapy, deliver a high dose of radiation to the tumor with a steep dose gradient that limits dose to adjacent normal tissues. The Maastro applicator is a novel endorectal applicator developed for use with conventional HDR afterloading systems (Ir-192), intended to achieve a contact-like dose distribution using widely available HDR technology. Although dosimetric and simulation studies support its technical feasibility, prospective clinical evidence remains limited, motivating this Phase II evaluation.
Eligible participants will be adults (≥18 years) with rectal cancer whose tumors are accessible and suitable for endorectal HDR brachytherapy using the Maastro applicator, and who are deemed able to undergo the procedure with sedation/anesthesia as appropriate. Key exclusions include active inflammatory bowel disease (moderate-severe flare) or severe anorectal conditions that preclude safe applicator placement.
Participants will undergo standard baseline assessment per institutional practice, including clinical evaluation and appropriate imaging and/or endoscopic assessment. The Maastro applicator procedure will be performed in a controlled procedural environment. Tumor localization and applicator positioning will be guided by direct endoscopic visualization and transrectal ultrasound (TRUS) as applicable. HDR treatment plans (including applicator selection and relevant planning parameters) will undergo institutional verification and safety checks prior to delivery. Radiation will be delivered via an HDR afterloader through the applicator to the intended target volume. Patients will be observed post-procedure for immediate complications and provided standardized post-procedure instructions.
Participants will be followed at predefined intervals to assess tumor response, toxicity, and patient-reported outcomes. Tumor response will be assessed using clinical evaluation and imaging and/or endoscopy, with biopsy performed when clinically indicated. Adverse events will be captured and graded using CTCAE v5.0, including both acute and late gastrointestinal and genitourinary toxicities. Quality of life will be assessed longitudinally using validated instruments (EORTC QLQ-C30 and EORTC QLQ-CR29). Additional clinical endpoints include local control, regional control, progression-free survival, and overall survival. Exploratory analyses will assess associations between dosimetric parameters and tumor control and/or toxicity.
The primary endpoint is the clinical complete response rate following Maastro applicator HDR brachytherapy. Secondary endpoints include disease control outcomes (local/regional control, progression-free survival, overall survival), incidence of acute and late toxicities, and changes in quality of life over time. The planned sample size is 25 patients, consistent with a Phase II pilot cohort intended to generate early safety and efficacy signals and inform subsequent larger studies and protocol refinement.
