ICRU 38 & 89 Concepts in Brachytherapy of Cervical Cancer
Tata Medical Center, Kolkata
Why these reports ?
| ICRU 38 (1985)(ICRU 1985) | ICRU 89 (2013)(ICRU 2013) |
|---|---|
| Harmonize terminology and definitions between BRT and EBRT | Advances in dose rate, treatment planning and imaging |
| Dose absorbed by target volume at one or more reference point not meaningful (high dose gradients) | Enable volumetric dose reporting and introduce an adaptive target concept |
| Transition from Radium based systems to other isotopes | Transition from a point based to a volume based approach |
Revision of concepts
What is the difference between Target volume, Treated Vol and Irradiated Vol ?
Which of these concepts are oncological
Which of these concepts are related to the treatment plan ?
Which of these concepts relate to “dose tolerance”
Outline of Report
ICRU 38:
Definition of terms and concepts
Recommendations for reporting absorbed doses and volumes
Time dose pattern
ICRU 89 (whats additional)
Brachytherapy imaging for treatment planning
Tumor & Target volume and adaptive radiotherapy
OAR and morbidity related concepts and volumes
Radiobiological considerations
Dose and volume parameters for reporting
Volumetric dose assessment
Pre-ICRU 38: Stockholm System
Delivery of large doses of 20 - 30 hr separated by 1 - 2 weeks
As amount of Ra used was larger application times were lower
Uterus : 30 - 90 mg of Ra
Vagina : 60 - 80 mg of Ra
Large selection of applicators
Limited use of EBRT
TRAK with 3 hours of application ~ 78 mGy
Pre-ICRU 38: Paris System
Prescribed a fixed mass of Ra for a given tumor volume
Premise: Dose at any point ∝ source strength x implant time
Longer time of irradiation (Regaud )
120 hours (5 days) -> 7200 - 8000 mgh Ra
Equal uterine and vaginal loading
Combined with orthovoltage EBRT
Approx TRAK after 144 hours = 57.9 mGy
Pre-ICRU 38: Manchester System
Key innovation: Determine loading patterns which would result in SAME dose to predetermined points in the pelvis
Specification of brachytherapy in terms of the absorbed dose not source loading time and source activity
Defined points: Point A and B. Hypothesized that dose to point A is “dose-limiting”
Two applications of 72 hrs with 4 - 7 days interval. Dose of 8000 R at 55.5 R/hr at point A
Radiographs to verify applicator position
EBRT to cumulative point B dose of 6000 R (3000 R from brachy). Usually midline shielding used
Approx TRAK after 144 hours = 67.5 mGy
Key reasons for ICRU 38
Change in type of radio-isotopes
Increased specific activity allowing different dose rates
Source configuration change : Linear source (tubes) -> point source (beads / pellets / cylinder)
SI unit usage
Computerized treatment planning being used
ICRU38: Specification of Radioactive Source
Kerma : Kinetic energy release per unit mass.
Reference Air Kerma Rate (KR) : Kerma rate to air in air at a distance of 1 m corrected for air attenuation and scattering
Total reference air kerma rate: Sum of products of RAKR and duration of application for each source.
Note
Note that ICRU 72 has a slightly modified defintion of RAKR for brachytherapy. As very low energy photons can be produced due to “characteristic x-ray emissions” from source encapsulation these low energies are EXCLUDED from the calculation.
The energy threshold is 5 KeV for low energy sources (Pd103 and I125) and 10 KeV for higher energy sources (Ir192 and Co60).
TRAK: Reasons for adoption
- Unambiguous quantity as compared to mghr of Radium
- Easy to calculate
- Proportional to integral dose to patient
- Allows approximation of the absorbed dose delivered during treatment at distances of 20 - 10 cm.
- Useful index for radiation protection of personnel
Note
TRAK is also an accurate surrogate for isodose volumes like the 60 Gy, 75 Gy and 80 Gy isodoses. (Nkiwane et al. 2017)
TRAK however is a physical measure and not correlated with biological outcomes. It is also dependant on the fractionation schedules (e.g. PDR TRAK >> HDR TRAK).
ICRU 38: Reference Volume
Proposed tissue volume encompassed by an isodose to be the reference volume.
Reference isodose : 60 Gy (derived from LDR)
Note that treatment volume ≠ reference volume. Treatment volume in brachytherapy is different from EBRT as the dose gradient is high and shape of the volume depends on the technique.
In brachytherapy target volume should be included in the treatment volume
In ICRU 38 in addition to the reference dose the parameters to describe the “pear shaped” reference volume were introduced.
ICRU 38: Absorbed dose at Reference points
| Located near the target volume | Located away from target volume |
|---|---|
| Bladder reference point | Lymphatic trapezoid |
| Rectal reference point | Pelvic wall reference point |
Important
Please note that the definitions provided in ICRU 38 for these points are applicable when planning is performed on orthogonal planar radiographs. They are not applicable for other forms of planning.
ICRU 89: MRI Imaging
One of the most key advances in the entire system.
Delineation of GTV at the time of treatment initiation (GTVinit) and brachytherapy (GTVres) possible.
Forms basis for delineation of high risk and intermediate risk CTV.
T2w sequences most useful for the delineation of these volumes.
Note
Per fraction imaging is recommended by ICRU as inter-fraction variation in doses to the target and OAR can be quite high (~ 10% and 20% respectively). These result in a dose uncertainty of 2 - 4 Gy EQD2 for target and 4 - 8 Gy for the OAR.
ICRU 89: Target volume concepts (GTV)
GTV-Tinit: Initial macroscopic tumor demonstrable on imaging (GTV-Tinit/mri) and examination (GTV-Tinit/clin).
GTV-Tres: Residual macroscopic tumor demonstrated on imaging and examination during brachytherapy:
The GTV-Tres is defined by imaging and examination but not confirmed pathologically.
Typically reduces by 60 - 80% as compared to GTV-Tinit . It may not be present if there is a complete response post EBRT (~ 5- 10%)
Tip
Note that the “yT” designation is not used as in patients undergoing brachytherapy post EBRT to designate tumor as there is NO pathological assessment.
Example: GTV-Tinit
Initial GTV-T
Example: GTV-Tres
Residual GTV
ICRU 89: Target Volume Concepts (CTV)
CTV-T: Clinical target volume around the tumor with subclinical disease as it spreads along anatomical pathways and limited by anatomical barriers:
CTV-T1 : Entire cervix
CTV-T2 : Margins around cervix with significant probability of disease involvement
CTV-T3 : Areas of potential spread e.g. parametrium, upper third vagina, uterus.
CTV-Tres : Adaptive CTV around GTV-Tres. This adaptation is the key innovation and reason behind the success of image guided brachytherapy. The type of adaptive CTV-Tres used in image guided brachytherapy is a specific type where the GTV-Tres is treated along with residual pathological tissue in the regions previously occupied by the GTV-Tinit.
ICRU 89: Target Volume Concepts (CTV)
| Stage | CTV Description |
|---|---|
| IA2 - IB | CTV-T: Whole cervix is the CTV-T |
| IB1- IV | CTV-T1: Whole cervix |
| CTV-T2: 10 mm margin into the uterus, vagina, parametria. 5mm expansion into the anterior cervix-bladder and posterior cervix-rectum space | |
| CTV-T3: Parametria, uterine corpus, upper vagina |
Note
CTV-T2 ≃ CTV-HR (ESTRO) while CTV-T3 ≃ CTV-IR (ESTRO). Typically for all cases where EBRT is required, CTV-T3 is the target volume.
Example: CTV-Tinit
PreEBRT CTV
ICRU 89: Target Volume Concepts (CTV)
The CTV-THR is the high risk CTV at the time of brachytherapy. This has the highest burden of residual disease and is at the greatest risk of relapse
Comprises of the following:
Entire cervix, residual palpable disease, visible mucosal changes, pathological induration, residual gray zones (MRI).
To be included have to be present in the GTV-TInit.
Gray zones : Zones which were signal intensive in initial MRI but at pre-brachy MRI have become “gray” indicating pathological residual fibrotic disease. Always within GTVInit and always defined with MRI.
The CTV-TIR is the intermediate risk CTV corresponding to the GTV-Tinit, the CTV-THR and a margin around the CTV-THR. Margins are applied around the CTV-THR to account for areas of significant microscopic disease
Example: CTV-THR
Example: Gray Zone
Gray Zone
Example: CTV-THR
Example: CTV-TIR
ICRU 89: Target Volume Concepts (PTV)
Setup uncertainties in brachytherapy are different from EBRT.
Most are related to applicator reconstruction and are within 1 - 2 mm.
Cranio-caudal movement along the applicator axis is probably the largest source of uncertainty.
However, this uncertainty does not have a impact on the dose through the target. Longitudinal margins may be considered along the axis of the tandem - but not orthogonal margins.
ICRU 89: Treatment Related Morbidity
| OAR | Endpoints | Dose Volume Relationship |
|---|---|---|
| Bladder | Urgency and Incontinence | Trigone and bladder neck |
| Increased muscle tone, fibrosis, volume shrinkage | Whole bladder wall | |
| Rectum | Bleeding (related to telengiectasia), ulceration | Rectal mucosa |
| Change in bowel habits | Circumferential absorbed dose | |
| Urgency and continence | Recto-anal and sphincter dose | |
| Vagina | Vaginal telengiectasia, shortening, stenosis, mucosal pallor, reduced rugae | Vaginal dose at different segments |
ICRU 89: OAR FSU organization
| Serial Behaviour | Parallel Behaviour |
|---|---|
| Transport function of rectum, rectosigmoid, bowel, ureter, urethra | Rectal vessels and wall organization (localized ulceration and bleeding) |
| Vaginal stenosis and fibrosis | Telengiectasia, reduced rugosity, ulceration and adhesions |
| Bladder outlet obstruction functions | Bladder filling function |
Note
Understanding the FSU organization and relation to toxicity endpoint useful to understand which dose volume metrics will matter for the toxicity. For serial FSU damage the small volume (2 cc) and very small volume (0.1 cc) doses are important.
Important
Contouring of the entire organ acceptable for these small volumes. However for larger volumes (> 3 cc) contouring of the outer wall is needed.
ICRU 89: Additional considerations for OAR
For key brachytherapy endpoints, small volume doses matter
PRV is not recommended as even small shells around the OAR will result in huge changes in small volume doses
Intra-fraction changes in the volumes can be minimized by adopting a “bladder protocol” and ensuring an empty rectum.
Inter-fraction changes are always significant and recommended measure is to repeat imaging at each fraction.
Cumulative doses are calculated by assuming that the same volume is irradiated to the highest absorbed dose for all fractions of the brachytherapy.
ICRU 89: Concept of EQD2
\[ \frac{\left(D*\left(1+\left(\frac{d}{\left(\frac{\alpha}{\beta}\right)}\right)\right)\right)}{\left(1+\left(\frac{\alpha}{\beta}\right)\right)} \]
EQD2 = Equieffective doses at 2 Gy per fraction. Reported in Gy. Based on the LQ model.
⍺/𝛃 parameters recommended are 3 for OAR dose and 10 for target. T1/2 values for early endpoint is 1.5 hours. (note that the repair half time is quite controversial). Recovery between fractions (when using HDR) is considered complete
ICRU 89: Dose and Volume Parameters
Current definition of point A : 2 cm superior to the upper surface of the vaginal applicator and 2 cm lateral to the intra-uterine tandem in the plane of the uterus
Point A dose is a surrogate of a minimum target dose to a cylinder of 4 cm and height less than the loaded length of the tanden for ICA.
Point A doses are not related to contouring and therefore useful for inter-departmental comparisons.
Issues with brachytherapy DVHs:
Steep and heterogenous dose distribution: single point is not enough (e.g. median dose).
Difficulty in determining which DVH parameter is related with a clinical effect
ICRU 89 : Dose Volume Parameters (CTV)
D90% : Minimum doses delivered to 90% of the target.
Less affected by random uncertainties in target volumes.
However can be high even when parts of volume receive a very low dose.
D98% (Near minimum dose) : Minimum dose to 98% of the target volume
Less susceptible to contouring uncertainties and volume sampling for dose calculation as compared to D100%.
Recommended for IMRT doses also.
D50% (Median dose): Minimum dose to 50% of the target volume.
Reflective of the very high doses delivered near the applicator.
These intentionally high doses are believed to be responsible for the high control rates due to brachytherapy.
Radibiological calculations are not straightforward as for very high doses per fraction LQ model may not hold.
ICRU 89: Dose Volume Parameters (OAR)
Small volume doses (2 cc and 0.1 cc) are recommended to act as constraints for endpoints like necrosis, bleeding, ulceration and fistula.
D2cc = Minimum dose to 2 cc volume of the structure. D0.1 cc (near maximum dose) is the minimum dose to 0.1 cc volume.
Important to note that these are NOT point doses but extend for a distance of 10 - 30 mm on the surface of the structure
As these are areas over the wall they may not be “contiguous” especially in case of sigmoid.
Volume may be underestimated based on it’s partition into organs. Hence anatomical evaluation of the doses should be done.
ICRU 89: Dose Volume Parameters (Prescription)
Traditionally brachytherapy doses are prescribed to a reference point (e.g. Point A).
Planning aim dose is the dose which is aimed by the physician before the planning is started while Prescription dose is the achieved dose after the planning is done.
ICRU 89 allows volumetric specification of the prescribed dose (usually D90). The prescribed dose is reported in EQD2 and the final prescribed dose is a summation of both EBRT and brachytherapy doses.
ICRU 89: Applicator Reconstruction
Applicator reconstruction is associated with uncertainities arising from applicator type, imaging modality, image parameters and image registration.
Creating a library of fixed geometry applicators after proper auto-radiography minimizes errors in reconstruction.
Reconstruction in CT is easier as compared to MRI as specalized channel markers are required for MRI (usually fluid filled which change over time).
Aditionally slice thickness plays a role in the accuracy and thickness < 5 mm is recommended.
Note
While the intrauterine portion of the applicator is typically a part of the CTV, it is recommended that the vaginal ovoids / ring and packing are NOT included in the CTV.
ICRU 89: Reference Points & Registration
Point A : Defined w.r.t uterine plane and requires rotation of the image plane in multiplanar images. The axis is aligned with the tandem of the uterus.
Bladder point: Requires placement of contrast (7 cc) in the balloon of the Foley’s. The point needs to be defined on the posterior most aspect of the balloon on the axial slice where the center of the balloon is located.
Recto-vaginal point: Is located 5 mm behind the posterior vaginal wall on an AP line drawn from the middle of vaginal sources (identified on the axial section which passes through this plane).
Image registration: Rigid registration of the applicator in image sequences recommended, However for each 1 mm of the registration error, 4% - 6% error in DVH parameters will occur. Typically needed with volume segmentation and applicator reconstruction are done in different images.
ICRU 89: Treatment Planning (Optimization)
The key principle is to retain the high dose sleeve around the central tandem. This leverages the high radiation tolerance of the uterus and also ensures highest dose to the cervical tumor.
For scenarios where CTV-THR does not reach the uterine corpus, modifying dwell positions in the uterus can avoid dose to the sigmoid and bowel.
However this dose should not be made completely 0 to account for the cranio-caudal uncertainity in the applicator reconstruction.
Typical loading patterns to ensure spatial geometry of the dose distribution is not much altered:
60% of the total dose from intrauterine tandem
40% of the total dose from the vaginal sources
If needles are used about 10% - 20% of the total loading
Summary
ICRU 38 and 89 - harmonize reporting for intracavitary brachytherapy in cervical cancer
Reflective of the incremental advances made in brachytherapy treatment - sources, dose rates, imaging modalities, adaptive radiotherapy and radiobiological understanding
Current system is increasingly moving towards a volumetric approach with evidence for improved control and reduced toxicity as a consequence.