Endoscopic Evaluation of Late Rectal Injury Following CyberKnife Radiosurgery for Prostate Cancer

Stage II Prostate Carcinoma Clinical Trial

Official title:

Prospective Endoscopic Safety Evaluation of Late Rectal Mucosal Injury Following CyberKnife Radiosurgery for Clinically Localized Prostate Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01618838
• Other study ID #: IRB 2009-474
• Status: Terminated
• Phase: N/A
• Start date: February 2011
• Est. completion date: December 2012

Study information

• Verified date: August 2018
• Source: Georgetown University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Radiation therapy is a well-established treatment modality for clinically localized prostate cancer. Men who choose to undergo radiation treatments for prostate cancer will have to live with the side effects for many years. Attempts have been made to protect surrounding tissues while delivering high dosage of radiation to cancer. With the rectum being so close to the prostate, many patients still suffer from side effects caused by radiation injury to the rectum, especially those who received conventional external beam radiotherapy.

CyberKnife is an FDA approved radiosurgical devise. Its flexible robotic arm allows radiation beams to be delivered in different directions, providing a highly conformal, uniform dose with steep dose gradients. Therefore, treatment with the CyberKnife radiosurgical system should minimize the toxicity to the surrounding structures. CyberKnife System also incorporates a dynamic tracking system to allow the robot to correct the targeting of therapeutic beams during treatment. These improvements allow for dose escalation within the prostate with less normal tissue toxicity.

The purpose of this study is to estimate the proportion of patients with endoscopically detectable telangiectasia as the indication of radiation injury to the rectum, after CyberKnife Treatment for prostate cancer.

Description:

Radiation therapy is a well-established treatment modality for clinically localized prostate cancer. Current techniques include conventional external beam radiotherapy and intensity modulated radiation therapy (IMRT). The efficacy of conventional external beam radiation treatment (60-70 Gy in 2 Gy fractions) using several uniform fields has been documented. The 10-year disease-free survival rate for patients with disease confined to the prostate in the pre-Prostate Specific Antigen (PSA) era was approximately 50-70%. Analysis of these data suggested that dose escalation could improve local control in prostate cancer.

On average, men who choose to undergo radiation therapy treatments for prostate cancer will have to live with the side effects of therapy for many years. Chronic proctitis may occur after radiotherapy (RT) to the pelvic region. According to a published series, it clinically occurs after radiation therapy of localized prostate cancer at a frequency of 5-20%. It occurs months to years after treatment (average 8-12 months) with a large majority within two years following radiation therapy. Patient characteristics, such as a history of inflammatory bowel disease or chronic anticoagulation therapy, may increase an individual patient's risk of clinically significant proctitis. Patients with radiation-induced proctopathy have described symptoms of rectal pain, diarrhea, urgency, rectal bleeding, and increased frequency of bowel movements. Endoscopic evaluation shows telangiectasia, congested mucosa and ulcers. Rectal bleeding occurs from the neovascular telangiectasia seen in about 60% of patients receiving conventionally fractionated radiation therapy. The other symptoms probably develop from the decreased rectal compliance associated with rectal wall fibrosis. These symptoms are, in current reports, most often classified according to the NCI Common Toxicity Criteria grade for late gastrointestinal side effects. Due to the proximity of the rectum and bladder to the prostate, using conventional techniques, the prescription dose is limited to 65-70 Gy. Although attempts were made to protect the rectum, the incidence of rectal bleeding was unacceptable at doses greater than 70 Gy (20%).

The risk of proctitis and rectal bleeding appeared to be dependent upon both the radiation dose and the volume of the rectum in the high dose area. Radiation Oncologists' efforts to optimize the therapeutic ratio for prostate cancer treatment have therefore been directed toward limiting the high dose volume to the prostate while escalation the dose within that volume. Intensity modulated radiation therapy (IMRT) is a widely used technology to achieve this goal. It is accomplished by modulating the radiation beam intensity within each radiation field in accordance with an optimization algorithm. This has allowed greater dose-escalation without evident increase in acute complications, although follow-up is too short to fully assess control and complication rates. Whether IMRT will provide a degree of conformity that proves to eradicate prostate cancer with a high probability while sparing local structures is as yet unresolved.

Late Rectal Mucosal Injury Following CyberKnife RadioSurgery for Clinically Localized Prostate Cancer. The type, extent and incidence of rectal mucosal injury following CyberKnife radiosurgery are currently unknown. The severity of clinical proctitis following radiation therapy is commonly documented using the NCI Common toxicity criteria/Radiation Therapy Oncology Group/EORTC. Unfortunately, clinical proctitis has a low sensitivity for detecting rectal mucosal injury. Endoscopy gives the most accurate estimate of the extent and incidence of rectal mucosal injury. The Vienna rectoscopy score (VRS) was developed to quantify rectal mucosal changes following radiation therapy. In this study, endoscopic evaluation of mucosal damage from CyberKnife treatment will be documented and correlated with gastrointestinal side effects and treatment planning parameters.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate (Biopsy within one year of enrollment)

• Signed Study-Specific Consent

• PSA within 60 days of registration

• Baseline American Urological Association (AUA)/ International Prognostic Scoring System (IPSS) score of < 20

• Candidate for screening colonoscopy

• Pretreatment Colonoscopy/lower endoscopy done

Exclusion Criteria:

• Prior pelvic radiotherapy

• Prior radical prostate surgery

• Recent (within 5 years) or concurrent cancers other than non-melanoma skin cancer

• Implanted hardware adjacent to the prostate that would prohibit appropriate treatment planning and/or treatment delivery

• Inflammatory bowel disease

Related Conditions & MeSH terms

• Prostatic Neoplasms
• Stage II Prostate Carcinoma

Intervention

Radiation:
• CyberKnife radiosurgery
Treatment Planning: Inverse planning using the CyberKnife planning system will be employed. The treatment plan used for each treatment will be based on an analysis of the volumetric dose including dose-volume histogram (DVH) analyses of the Planning Treatment Volume (PTV) and critical normal structures. The homogeneous CT model shall be used. Number of paths and beams used for each patient will vary and will be determined by the selected individual treatment plan. To reduce overall treatment time and total monitor units, 150-200 non-zero beams are recommended. No more than 250 beams shall be employed. Tuning structures shall be employed to minimize conformality index (CI) and new conformality index (nCI), preferably yielding values less than 1.20 and 1.25, respectively.

Locations

Country	Name	City	State
United States	MedStar Georgetown University Hospital	Washington	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Georgetown University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients With Endoscopically Detectable-telangiectasia (VRS Grade 1 or Higher).	Telangiectasia is the primary outcome since it is a measure of tissue fibrosis (primary source of proctitis) and is a well-defined and measurable outcome.; No patients had outcome before the trial was terminated.	Planned for 7 years, collected up to 23 months
Secondary	Proportion of Patients With Rectal Bleeding.		Planned for 7 years, collected up to 23 months
Secondary	Progression-free Survival	Progression-free survival will be defined as the time in months from study entry until progression or death. Patients who are alive and free from progression on the date of closing follow-up will be censored on that date. Data table reports the number of participants who were alive without progression at the end of the study.	Planned for 7 years, collected up to 23 months