Surgical access not facilitated- residues of hydrogel.

For advanced rectal tumors, the standard of care is neoadjuvant radiotherapy (RT) +/- chemotherapy followed by surgery 8-10 weeks later. Despite its proven efficacy in reducing local relapse, the neo-adjuvant treatment has been associated to non-negligible side effects, especially in terms of impaired sexual function. For females, pelvic RT is frequently associated to long-term complications such as vaginal stenosis (VS), vaginal dryness, and dyspareunia, while in men RT doses delivered to the neurovascular peri-prostatic bundles and penile bulb have been associated to the risk to develop erectile dysfunction.

In prostate cancer, hydrogel spacers have been evaluated to create space between the target (prostate) and the organ (rectum) to be spared during radiotherapy treatments. Clinical studies have shown the ease of spacer application; patient tolerance and, good clinical outcomes (decrease in rectal toxicities).

This pilot study wishes to investigate feasibility and efficacy of the injected hydrogel spacers TraceIT® in sparing vagina/prostate in the treatment of rectal cancer patients.

This is a feasibility prospective pilot study. Ten patients (5 males and 5 females) with a histologically proven locally advanced rectal cancer with the indication of neoadjuvant radiotherapy or radio-chemotherapy will be recruited for this study. Prior to enrollment, potential candidates will undergo a thorough physical and clinical examination and documentation on medical and surgical history. If eligible, a baseline planning computed tomography (CT) simulation will be performed at the Radiation Oncology Department before the TraceIT® implant. Participants will undergo a transperineal injection of TraceIT® spacer gel between rectum and vagina or prostate performed by a trained radiologist under transrectal ultrasound guidance. A CT simulation will be repeated within 3 to 5 days post injection using the same imaging modality and treatment position used the pre- TraceIT® injection. Radiation treatment plans will be generated using scans realized pre- and post- TraceIT® injection and compared using dose volume histograms (DVH) analyses. Tolerance, side effects, and adverse events related to the procedure will be recorded prospectively from the injection until week-4 after EBRT (External Beam Radiation Therapy) completion. Radiological status of the spacer will be evaluated on the preoperative magnetic resonance Imaging (MRI). Histopathological results and any serious and/or unanticipated adverse events following surgery procedure will be recorded retrospectively.

Inclusion Criteria:

• WHO (World Health Organization) performance status 0-1 at registration
• Locally advanced (T1-2 node positive or T3 N0/N+) histologically proven rectal adenocarcinoma located in the middle or in the high rectum. Patients with tumors located in the lower rectum may be eligible if the location of the tumor do not preclude the implant of the spacer (i.e. tumors located anteriorly in the proximity of the anal sphincter)
• Indication for preoperative radiotherapy or radio-chemotherapy
• Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
• Before patient registration/randomization, written informed consent must be given according to GCP/ICH (Guideline for Good Clinical Practice/Harmonised Tripartite Guideline), and national/local regulations.

Exclusion Criteria:

• Patient <18 years old
• WHO performance status ≥ 2 at registration
• Patient with a local extension, clinical stage T4 and/or presenting a vagina/prostate/bladder invasion
• Active bleeding disorder or clinically significant coagulopathy (PTT >35sec/ or INR >1.4 (INR, international normalized ratio). Or platelet count < 100'000/mm3)
• Active inflammatory or infectious process involving the perineum, gastrointestinal or urinary tract
• Compromised immune system (e.g. HIV/acquired immunodeficiency syndrome, autoimmune disease or immunosuppressive therapy)
• History of previous pelvic surgery
• History of active inflammatory bowel disease (Crohn's disease, ulcerative colitis, irritable bowel disease)
• Contraindication for MRI
• Pregnant or lactating females
• Inability to provide a written informed consent
• Inability to comply with study and follow up procedures