Dose Escalation Using Fiducial Markers in Image Guided Volumetric Modulated Arc Therapy to the Focal Lesion Micro Boost of Localized Prostate Cancer

NCT03384199 | Completed Phase 2

• 1 other identifier: Prostate
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Gold markers implanted in the prostate are used frequently for position verification of the prostate during external-beam radiotherapy. By using the markers as a surrogate for the prostate itself, not only set-up errors, but also the internal motion of the prostate relative to the bony anatomy can be identified. It is thus believed that escalated dose marker guided radiotherapy should result in better biochemical control compared to conventional external beam radiotherapy, with a similar or lower incidence of toxicity. However, clinical data to support this is still limited. The purpose of this study is to directly compare late toxicity as well as biochemical control between patients treated with dose escalated marker guided radiotherapy versus conventional dose non-marker guided radiotherapy who has otherwise been treated with similar radiotherapy planning techniques and equipment. Prostate magnetic resonance imaging has undergone several technical improvements and shows promises for prostate tumor detection and localization. In addition to morphological information, magnetic resonance imaging allows an estimation of physiological properties of tissues. Diffusion-weighted magnetic resonance imaging is sensitive to restriction of diffusion of water molecules, and dynamic contrast enhanced magnetic resonance imaging can analyze tissue micro vascular properties. Multi para metric magnetic resonance imaging combining Diffusion-weighted and Dynamic contrast enhanced has demonstrated its value in distinguishing malignant from benign prostate tissue. Higher radiation dose levels were consistently associated with improved biochemical control outcomes and reduction in distant metastases. Radiation dose was one of the important predictors of long-term biochemical tumor control. Dose levels \< 70.2 Grey and 70.2-79.2 Grey were associated with 2.3 and 1.3-fold increased risks of pro static specific antigen relapse compared with higher doses. However, further dose escalation to the whole gland is limited due to an unacceptable high risk of acute and late toxicity. Moreover, local recurrences often originate at the location of the macroscopic tumor, so boosting the radiation dose at the macroscopic tumor within the prostate might increase local control. A reduction of distant metastases and improved survival can be expected by reducing local failure. Treating the dominant focus or boosting the dose to this area while reducing the dose to as much healthy tissue as possible has significant potential for improving treatment.

Conditions

Prostatic Adenocarcinoma

Keywords

Localized Prostate; VMAT; Dose escalation; Fiducial marker; Focal Lesion; Random error during dose escalation radiotherapy; fiducial marker image guided technique

Outcome Measures

Primary Outcomes (1)

• Measurement of systemic error in mm and random error in cm in the different three direction X-Y-Z

  Position verification will be done guided with implanted gold markers with daily portal imaging (AP \& lateral) correction protocol in mediolateral, superior-inferior \& inward-outward directions by mm for 35 fraction. The off-line portal pre-correction images will be verified daily to detect average shifts in the three diresctions. Random or inter-fraction errors which are deviations between different fractions will be taken weekly during a treatment series. Systematic errors Which are deviations between the planned patient position and the average patient position of a course of fractioned therapy will be taken in the first three settings. The mean and standard deviation (SD) of the systematic error and SD of random errors will be analyzed.

  12 months

Secondary Outcomes (3)

• Biochemical relapse of PSA above normal level 4 ng/dl

  12 months

• subjective toxicity assessment

  12 months

• Objective toxicity assessment

  12 months

Study Arms (1)

Dose escaltion

EXPERIMENTAL

insertion of 3 fiducial markers, prostate will receive 78 Gy with dose escalation to prostate focal lesion up to 87 Gy

Radiation: Dose escalation to prostate focal lesion

Interventions

Dose escalation to prostate focal lesion RADIATION

For each patient the radio-opaque marker (used for treatment verification) will be inserted by ultrasound guidance \& local anaesthetic with an 17ga x 30cm brachytherapy needle that has 1.2mm x 3mm one gold marker. The ultrasound probe (as used for transrectal biopsy) will be introduced rectally with the patient in the left lateral position. After measuring the volume of the prostate and determining the desired position (preferably in the corpus of prostate), three gold markers will be inserted as follows: one into right side, one into left side of the base and the third in the apex of the prostate

Dose escaltion

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Performance status ECOG: 0-2
• Pathologically proven prostatic adenocarcinoma.
• Localized prostate cancer (Gleason's score: 2-10, Baseline serum prostatic antigen: \>4 ng/dl, T1a-T3b).
• No extra prostatic invading adjacent structures.
• Adequate hematological, renal \& hepatic profile.
• Insertion of more than one fiducial marker in the prostate.
• Patient did verbal \& written consent and adherence to treatment.

You may not qualify if:

• Patient weight \>130 kg.
• Performance status EGOG: 3-4.
• Distant metastasis.
• Previous pelvic radiotherapy.
• Previous prostatectomy.
• Urinary bladder stones.
• General contraindications for MRI (i.e. cardiac pacemaker, metal implants or history of severe allergic reaction after administration of contrast agent).
• Concomitant neoplastic disease or previous anti neoplastic therapy.

Sponsors & Collaborators

• Kasr El Aini Hospital: lead

Study Sites (1)

Radwa Fawzy Saleh Ahmed

Cairo, Maadi, 11728, Egypt

Location

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: assistant Lecturer of Clinical Oncology

Model Details: VMAT dose escalation protocol with image guided fiducial markers

Study Record Dates

• First Submitted: August 21, 2016
• First Posted: December 27, 2017
• Study Start: May 1, 2016
• Primary Completion: December 1, 2017
• Study Completion: April 1, 2018
• Last Updated: August 14, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share

Locations

EG (1)