Plan Evaluation in Plan Evaluation in Primary Brain TumoursPrimary Brain Tumours

Dr. Ashutosh MukherjiAssociate Professor,

Department of Radiotherapy, RCC, JIPMER

Indications for RadiotherapyASTROCYTOMAS: •Surgery is the mainstay of treatment, with 80% of low grade cerebral, cerebellar and spinal cord tumours; and 40% of diencephalic tumours amenable for complete surgical resection.

Indications for radiotherapy:•In low grade tumours following incomplete resection in areas where tumour progression would compromise neurological functions.•Patients with progressive and / or symptomatic unresectable disease Radiotherapy is otherwise not indicated after complete resection in low grade astrocytomas.•Post operative radiotherapy is indicated IN ALL CASES OF HIGH GRADE GLIOMAS•In optic nerve gliomas, progressive disease on chemotherapy or after surgery in children older than 10 years.

Indications for Radiotherapy (contd)

Brainstem Gliomas•Rare patients with high grade gliomas.

•Patients with low grade gliomas with progressive post op.

•Surgically inaccessible tumours.

•Diffusely infiltrating gliomas of the pons.

ASTROCYTOMAS OF SPINAL CORD:

•Older children with low grade gliomas with post op progressive disease

•Surgically inaccessible tumours.

•Diffusely infiltrating / high grade gliomas.

Indications for Radiotherapy (contd)

• EPENDYMOMA: Post op RT indicated in all cases. Radiotherapy can be avoided in only the following situations: (a) Ependymoma of spinal cord post complete resection and (b) In selected supra-tentorial ependymomas involving non-eloquent areas resected with wide margins.

• CHOROID PLEXUS TUMOURS: Atypical tumours; Lepto-meningeal seedings (CSI to be given); Post op residual disease.

• CRANIOPHARYNGIOMAS / SELLAR TUMOURS: Sub-totally resected tumour or recurrence after total excision.

• PINEAL TUMOURS: Sub-totally resection; or leptomeningeal seedings.

• GERM CELL TUMOURS / GERMINOMAS: All cases.

Radiotherapy technique• For larger lesions opposed lateral fields

provide appropriate coverage.

• For smaller PTV a 3-field technique can provide a highly conformal dose distribution.

• IMRT can further improve dose conformality, but increase in treatment time is to be considered if anaesthesia is also being used in children.

• SRT uses a hypofractionated treatment schedule, & may be preferred for children.

Patient positioning: A neutral head position with the patient supine is easily reproducible. Noncoplanar beams can be used to avoid entry and exit dose to organs at risk (OAR).

• Immobilization: Variability of setup not more than 2-3 mm with thermoplastic mask. More accurate and/or rigid head positioning and immobilization can be obtained by a modified stereotactic head frame with noninvasive multiple-point head fixation.

• Patient is placed in the positioning device, and scanned, typically with radio-opaque reference markers placed at the setup isocenter.

• Verification films taken before treatment; and include orthogonal radiographs to verify the isocenter, + films of any custom-shaped portal fields.

• Simulation: patient is immobilised and scanned with three radio-opaque reference markers placed on the thermoplastic mask.

• A prone setup may be considered for posterior fossa tumors. • An optimum beam arrangement typically consists of 3 to 7 non opposed shaped

beams. When applicable, the contralateral uninvolved hemisphere of the brain should be spared as much as possible.

• A true vertex beam should be avoided, if possible, due to exit dose into the body; a 5 to 10 degree gantry rotation should be considered instead.

• Beams: Most lesions can be treated well with 4-6 MV photons• In case of infra-tentorial tumours, the posterior fossa must be boosted, with

the anterior border covering the posterior clinoids and the superior border including 1 cm above halfway between the foramen magnum and vertex (superior extent to tentorium cerebelli). Inferiorly, the field should cover the foramen magnum.

IMRT: improves dose delivery to target volumes and reduces dose to the dose-limiting OARs within the cranium. IMRT in craniospinal axis irradiation can homogenize dose and improve conformality.

Cranio-Spinal Irradiation: •OARs to be contoured include brainstem, temporal lobes, middle and inner ear. Decreasing dose delivered to cochlea and 8th cranial nerve in pediatric patients significantly reduces risk of hearing loss and is recommended for all patients receiving posterior fossa irradiation .

•The two opposed beams should be angled anteriorly. The inferior border of the initial cranial field is placed around C2-3. Depending on length, the spine is treated through one or two posterior fields.

•The field length of upper spinal field is maximised (40 cm at 100 cm SSD) and lower spinal field is minimized, to simplify junction shifts. The caudal border of the lower PA spine field is set inferior to S3 by a length equal to the two-field shifts, and then blocked back to S3.

• Accurate matching of upper border of the spine field to the lower border of the cranial field is required to avoid overlap in the upper cervical cord. All junction lines are moved 0.5 to 1.0 cm every 8 to 12 Gy to avoid overdosing or under dosing segments of the cord.

Radiotherapy doses and volumes• In general, low grade tumours require doses between 50 -54 Gy in

conventional fraction sizes of 1.8 Gy per day; while high grade tumours require 60 Gy @ 2 Gy per day.

• Ependymal tumours and PNET doses may differ; maximally between 50-54 Gy total dose. CSI dose is usually restricted to maximum 36 Gy (high risk) and 23.4 Gy (low risk).

• Germ cell tumours respond to doses of about 25 Gy; while lymphomas may require doses upto 30 Gy @ 1.5 Gy per day.

Contouring Guidelines

• Target volumes will be based upon CT or MRI.

• The initial gross tumor volume (GTV1) is defined and then margin added for clinical target volume (CTV1) and planning target volume (PTV1).

• Reducing PTV margins to modify organ at risk (OAR) dose is not advised. The OAR must be defined along with a planning risk volume (PRV) which is usually OAR plus 3 mm.

• GTV: Includes pre-op tumour volume on T2-Weighted MRI for phase 1 for low grade and T1 weighted post op contrast MRI for high grade lesions.

• CTV:

• PTV: 0.5 cm margin to CTV

1• In the event that an OAR is in immediate proximity to a PTV such that dose to the OAR cannot be constrained within protocol limits, a second PTV defined as the overlap between the PTV1 and the particular PRV of concern, is created.

• Dose to the PTV overlap must be as close as permissible to microscopic disease dose while not exceeding the OAR dose limit.

• The boost gross tumor volume (GTV2) is also defined along with boost clinical target volume (CTV2) and boost planning target volume (PTV2).

Goals of treatment planning

• prescription dose conforms to target volume– normal tissues are not excessively irradiated

• PTV receives uniform dose

• doses to OARs do not exceed tolerance values

Goals of treatment planning: PTV

• to ensure 100% PTV is covered by 95% of the prescription dose

• in other words, underdose to any part of PTV shall not exceed 5% of prescription dose

• to ensure overdose to any part of PTV shall not exceed 7% of prescription dose

Dose statistics provide quantitative information on the volume of the target or critical structure, and on the dose received by that volume. These include:- Minimum dose to the volume- Maximum dose to the volume- Mean dose to the volume- Dose received by at least 90-95% of the volume- Volume irradiated to at least 90-95% of the prescribed dose.

The following tools are used in the evaluation of the planned dose distribution:- Isodose curves- Orthogonal planes and isodose surfaces- Dose distribution statistics- Differential Dose Volume Histogram- Cumulative Dose Volume Histogram

Isodose chart or CT based 2D plan

evaluation

• Equivalent Square Field size (EFS) of each field is calculated. Any blocks used are deducted from this area by calculating the EFS of the blocked area also. The percent depth dose of each beam (PDD) is calculated using the EFS and prescription depth from standard tables.

• Then using standard formulae and percentage depth dose tables, the treatment time or number of MUs for each beam is obtained.

• This is multiplied with field weightage and wedge factors or tray factors (for blocks, etc) to correct it for beam weightage as well as for attenuation with use of modifying devices.

• The obtained isodose lines are then checked to see if they include the entire area under the field size as well as the extent of the 90% and 100% isodose line.

• Usually the 100% isodose line is shifted more towards the field surfaces with a narrow waist at the isocentre and it is usually reasonable to prescribe the dose to 90% isodose line.

• Dose is prescribed to the isodose which best covers the full target volume.

• In CT based 2D planning, dose is calculated for a given section and the isodose lines over the target volume reviewed.

• The isodose covering the target volume best with least dose variation in centre (higher isodose lines) is chosen.

• The disadvantage with this method is that the entire field size is assumed to match this one CT slice. This can be partially offset by choosing a few more slices representative of change in body contour and sequencing them as per their order in actual patient field length.

In 3D Planning, plan evaluation will involve:

Checking •Normalisation and normalised prescription dose.•Global dose maxima•Dose volume parameters of PTV and OARs.•Plan Sum of phase wise plans.•Brain and target volume coverage by prescribed doses and 50% isodose.•Hot and cold spots and their location and value•Conformity and homogeneity indices•DVH shape and distribution•Beam’s eye view and DRRs

Normalization

• after the dose calculation is over, the dose at some point has to be normalized to 100%

• this point can be anywhere in the grid

• user’s choice

Normalization Options

Check Global Dose Maximum

• what is its value?– not more than 107% for 3-D CRT– can be higher for IMRT, but within 115%

• where is it located?– it should be within CTV– preferably within GTV

Qualitative Evaluation Qualitative Evaluation MethodsMethods

Slice-by-slice evaluation

• review dose distributions in all slices

• whether a selected isodose level adequately covers the target volume or not– one has to select as high a isodose level as possible

• identification of hot spots / cold spots – location of these spots

Other display tools

Dose CloudDose Cloud

Quantitative Evaluation Quantitative Evaluation MethodsMethods

PTV

OAR

Dose statistics for volumes

Dose statistics for volumes• minimum dose– strong correlation between target minimum dose and

clinical outcome– high percentage of the dose maximum

• maximum dose– useful tool for critical structures– typically tolerance dose

• mean dose– indicator of dose uniformity within the target volume– should be very close to maximum dose

For Target Volumes• Target volume maximal dose ideally should

not be more than 5-7% of the prescribed dose and minimum dose to the target volume should not be less than 5% of prescribed dose.

• Inhomogeneity within target volume kept to ± 10% of the prescribed dose. ICRU 83 report is used for describing IMRT has described D98%, D50%, and D2%. (Dmax, Dmedian and Dmin)

• Dmax are checked in the dose colour wash in each slice to note its location; whether it is within the PTV as well as volume of the brain getting a dose 50% of prescription dose.

For OARs

• In case of serial OARs, their Dmax is checked as to whether it is limited to within tolerance doses.

• In parallel OARS Dmean is seen for analysis. Dmax is also noted to check for any undue hot spots.

• Check plan sum of all phases of the treatment plan to ensure once more that all dose parameters are within prescribed limits.

Dose Volume Histogram (DVH)

• most important evaluation tool for 3-D planning

• graphical summarization of 3-D dose distribution

• Represents a frequency distribution of dose values within a defined volume that may be the PTV itself or a specific organ in the vicinity of the PTV

Types of DVH

• cumulative– most used

• differential

• dose and volume axes can be absolute or relative– 4 combinations

Cumulative DVH• The computer calculates

the volume that receives at least the given dose and plots this volume (or percentage volume) versus dose.

• Basically the area under curve is the volume of tissue getting a dose and the smaller this area, the better for an OAR.

• The tail of the curve should not ideally taper too much to the right as this will mean a smaller volume getting a higher dose.

As high a isodose level as possible…

• should cover a large volume as well (>95%)• provisional selection of this isodose level for dose

prescription

Let us prescribe at 96%...

• what difference does this make?

Prescription Dose 5500 cGy

What did we do?

• 5225 cGy is 95% of 5500 cGy• entire PTV should get 5225 cGy

100%96%

5500 cGy5225 cGy

Dose prescription

Plan Normalization

Differential DVHs

• nice tool for assessing PTV dose uniformity

Limitations of DVH

• no spatial information– where the hot / cold spot occurred– whether it occurred in one or several disconnected

regions

• DVHs cannot be the sole criterion for evaluating / disclosing the best plan

• interpretation of the plot can be subjective!

Possible scenariosBody

PTV

RI

Body

PTV

Body

PTV

RI

Body

PTV

RI

miss

spill

RI

Perfectly conformal plan…

• how much of PTV is covered?• how much is the spill?• how is the uniformity within PTV?

Coverage Factor

• tells you how much you miss on PTV

miss Body

PTV

RI

volume of PTV covered by RIvolume of PTV

volume of overlapping regionvolume of PTV

ideal value = 1

Conformity Index (CI)

• ratio of /• ratio of / • ideally = 1; but expect around 1.3 to 1.5• presently, inverse of the ratio is followed

Body

PTV

RIspill

tells you how much you spill outside PTV

Homogeneity Index (HI)

• measure of uniformity within PTV

• expressed as the ratio D2/D98

– D2 is the maximum dose received by at least 2% of the PTV

– D98 is the maximum dose received by at least 98% of the PTV

Homogeneity Index (HI)

Homogeneity Index (HI)

• D2 / D98 = 5830/5463 = 1.067

• for a typical 3-D CRT plan, it is around 1.07• for IMRT it should be ≤ 1.15

• D5 / D95 has also been used

A word of caution ...

• these are ratios...• and hence are relative

values...• one has to be cautious in

interpreting...

• for a 10 cc PTV, CI = 2 is acceptable

• but for a 400 cc ?

IMRT plan evaluation

• not very different from 3-D CRT – IMRT – most refined form of 3-D CRT

• trade-off between conformity and homogeneity– if priority is conformity, accept increased

inhomogeneity– priority is homogeneity, accept decreased

conformity

HOT and COLD spots

• three questions to ask about all hot and cold spots– volume? – magnitude?– location?

• is there a consensus to any of these questions in any tumor site?

Cold spots: Recommendations

• volume: <1% of PTV

• magnitude: underdosing exceeds 5% of the prescription dose

• location: periphery of PTV; never acceptable within the CTV

Hot spots: Recommendations

• volume: <15-20% of the PTV

• magnitude: overdosing exceeds 15% of the prescription dose– <15% volume at the 110% dose level– <1% volume at the 115% level

• location: within the CTV (preferably GTV); not acceptable on the periphery of PTV

Summary

Normalize correctly

Check Global Max

Select as high a isodose level as

possible

Prescribe

95% dose covers 100% PTV?

DVH analysis

CI and HI

Documentation

Absolute dose

• Thus benefits of conformal radiotherapy lie in:

ensuring protection of normal tissues and…….

achieving dose escalation to tumor volume.

• Technology has given us new tools to hit targets……….

• But to use it correctly depends on us.

Thank youThank you