RTOG 0321

PHASE II TRIAL OF COMBINED HIGH DOSE RATE BRACHYTHERAPY AND

EXTERNAL BEAM RADIOTHERAPY FOR ADENOCARCINOMA OF THE
PROSTATE

Tamara Eng
University of Wisconsin La Crosse
06/27/2016

RTOG 0321
Designed and developed by the Radiation Therapy Oncology

Group (RTOG)
Participating sites: 14 institutions in United States and Canada
Target Accrual: 110 patients
Current Accrual (May 26 2006): 129 patients
Activation Date: July 30, 2004
Closure Date: May 26, 2006

Purpose of RTOG 0321

Purpose
To estimate the rate of late grade 3 or greater genitourinary

(GU) and gastrointestinal (GI) adverse events (AE) following

treatment with external beam radiation therapy and prostate
high dose rate brachytherapy
Secondary Objectives:
Estimation of:
Acute grade 3 or greater GU and GI AE
Freedom from biochemical failure
Overall disease-specific survival
Clinical relapse

Develop a quality assurance process for HDR prostate

brachytherapy

Inclusion Criteria
Histologically confirmed, adenocarcinoma of the prostate,

clinical stage T1c-T3b, N0, M0

Zubrod status: 0-1
One of the following combinations of factors:
Clinical stage T1c-T2c, Gleason score 2-6 and PSA >10 but 20
Clinical stage T3a-T3b, Gleason score 2-6 and PSA 20
Clinical stage T1c-T3b, Gleason score 7-10 and PSA 20

No prior pelvic or prostate radiation or chemotherapy

Hormonal therapy
Consent form

Exclusion Criteria
Stage T4 disease
Lymph node involvement (N1)
Distant metastases (M1)
Prior radical surgery for carcinoma of the prostate
Prior pelvic or prostate radiation
Previous chemotherapy for prostate cancer
Previous hormonal therapy beginning > 120 days prior to

registration
Major medical or psychiatric illness
Prior TURP
Prior invasive malignancy
Hip prosthesis

Appropriate Control
Individuals meet all inclusion criteria
External beam radiation therapy only

Radiation Oncology Regimen

Combination of 2 radiation therapy treatment techniques
Split course external beam radiotherapy
HDR brachytherapy implant
Overall treatment course: less than 8 weeks

External Beam Radiotherapy

Planning Techniques
Conventional treatment planning
3D conformal treatment planning

Total Dose: 45 Gy
Dose per Fraction: 1.8 Gy
Fractions: 25
Prescribed to CA or highest isodose line encompassing PTV

External Beam Radiotherapy

Clinical Target Volume (CTV)
Based on pretreatment CT
Prostate + Seminal Vesicles
Whole Pelvis
2/3 PSA + [(GS-6) 10] > 15%

Planning Target Volume (PTV)

1 1.5 cm margin

HDR Brachytherapy
Before or after external beam radiotherapy
Total Dose: 19 Gy
Dose per Fraction: 9.5 Gy
Fractions: 2
1: Day of catheter placement
2: Within 24 hours

Prescribed to periphery of PTV

Goal:
Deliver prescription dose to at least 90% of PTV
Minimize dose to critical normal structures

HDR Brachytherapy
Definition of volumes:
ICRU Report 58: Dose and Volume Specification for

reporting interstitial therapy

CTV
T1c-T2b: prostate only
T3a-T3b: prostate + extra-capsular extension

PTV = CTV

HDR Brachytherapy Specifications

3D CT based brachytherapy treatment planning
Treatment planning CT
HDR afterloading catheters:
CT compatible
Placed with TRUS guidance
Minimum 14 catheters in CTV
Flexible cystoscopy
Fiducial marker seeds

HDR Brachytherapy Specifications

Catheter Adjustment
Catheter Removal
Post treatment

Critical Structures
Bladder and Rectum
Contours included outer most border of mucosa
Urethra
Contour included outer surface of Foley catheter
Critical
Structure

Constraint

Bladder

V75 <1cc

Rectum

V75 <1cc

Urethra

V125 <1cc

Example Implant
Dotted Lines
PTV: dark blue
Rectum: fuchsia
Bladder: Yellow
Urethra: green

Solid Lines: isodose lines

125%: orange
100%: red
75%: yellow

Reprinted from Hsu I, et al. Phase

II trial of combined high dose rate
brachytherapy and external beam
radiotherapy for adenocarcinoma
of the prostate: preliminary results
of RTOG 0321. 20101

Criteria for Adverse Event

Adverse event (AE)
Graded according to:
Common Terminology Criteria for Adverse Events, Version
3.0

Acute AE period
9 months from start of protocol treatment

Late AE period
Starts from end of 9 months from start of protocol

treatment

Results
Published in 2010
AE data for 112 patients
Mean follow-up time 29.1 months:
3 acute grade 3 or greater GU/GI AE
4 late grade 3 or greater GU/GI AE

Estimated rate of acute grade 3-5 GU/GI AE

2.43%

Estimated rate of late grade 3-5 GU/GI AE at 18 months

2.56%

Results
ROI

Goal / Constraint

Results

PTV

Prescribed doseto at least 90% of PTV

Mean: V100 =94.7%

Range: V100 =87.6 - 98.9%
2 Cases: V100 <90%

Bladder

V75 <1cc

Mean: V75 =0.64 cc

Range: V75 =0 - 4.24 cc
18 Cases: V75 1 cc

Rectum

V75 <1cc

Mean: V75 =0.34 cc

Range: V75 =0 - 1.59 cc
8 Cases: V75 1 cc

Urethra

V125 <1cc

Mean: V125 =0.15 cc

Range: V125 =0 - 0.94 cc
0 Cases: V125 1 cc

Acute Adverse Events

GU/GI AdverseEvents
Urinary Frequency
Urinary Retention
Non-GU/GI AdverseEvents
Kidney Infection
Erectile Dysfunction

2
0
8

Grade
3
4
2
0
1
0

5
0
0

2
0
17

Grade
3
4
1
0
2
0

5
0
0

Late Adverse Events

GU/GI AdverseEvents
Urinary Retention
Cystitis
Urinary Incontinence
Proctitis

Non-GU/GI AdverseEvents
Proctalgia
Urogenital Hemorrhage
Rectal Hemorrhage
Anemia
Kidney Infection
Ejaculatory Disorder
Erectile Dysfunction

2
0
4
1
2

Grade
3
4
1
0
1
0
1
0
1
0

5
0
0
0
0

2
0
3
0
0
0
3
26

Grade
3
4
1
0
1
0
1
0
1
0
1
0
0
0
5
0

5
0
0
0
0
0
0
0

Conclusion
HDR boost for prostate cancer is feasible in multi-

institutional setting
The technique and doses used in this study resulted in
acceptable level of adverse events
Longer follow-up to determine efficacy of treatment
combination
Further research needed

Benefits
RTOG
First multi-institutional study of CT based HDR prostate
brachytherapy
Trial marked the arrival of image-guided brachytherapy for prostate
cancer
Offer improved treatment option for patients
Patients
Potential for medical benefit to patients
Potential of improved treatment outcomes and survival rate

References
1. Hsu I, Bae K, Shinohara K, et al. Phase II trial of combined high dose
rate brachytherapy and external beam radiotherapy for adenocarcinoma
of the prostate: preliminary results of RTOG 0321. Int J Radiat Oncol Biol
Phy. 2010;78(3):751-758. http://dx.doi.org/10.1016/j.ijrobp.2009.08.048
2. RTOG 0321 Protocol Information. Radiation Therapy Oncology Group
Web site.
https://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?
study=0321.
Updated March 11, 2014. Accessed June 14, 2016.
3. Hsu I, Hunt D, Straube W, et al. A dosimetric analysis of radiation
therapy oncology group (RTOG) 0321: the importance of urethral
dose.Pract Radiat Oncol. 2014;4(1):2734. http://dx.doi.org/10.1016/j.prro.2013.02.011

Thank you!