TOTAL BODY IRRADIATION(TBI)

Dr Venkata Krishna Reddy PPG RegistrarDept of Radiation Oncology

OVERVIEW

Concept Indications Doses Pre-requisites of TBI Performance of TBI in CMC Treatment Planning Toxicity Total Marrow Irradiation

HISTORY OF TBIYear Event

1907 X ray Bath

1940-1950 Lymphoma/Solid tumours with disseminated disease

1960 First exploration of BMT- Nobel Laureate E Donnall Thomas

1970-1980 TBI with low dose

1977 TBI Myeloabalative

2005 Total Marrow Irradiation

DEFINITION

When radiation is given in a way to cover the whole body, is called total body irradiation, or TBI.

CONCEPT OF TBI

One of main component in interdisciplinary treatment of hematological malignancies

Enables myeloablative high dose therapy (HDT) and immunoablative conditioning therapy prior to stem cell transplantation

High dose Therapy (HDT) Intensive chemotherapy High dose Total Body Irradiation (TBI) Transplantation of HLA compatible

blood or marrow stem cells (HSCT), and Supportive care under sterile conditions

during the aplastic phase.

Myeloablative therapy:

The irreversible elimination of the clonogenic malignant cells - therapeutic task of high dose TBI in treatment.

Immunoablative conditioning treatment:

The induction of immuno-suppression is the conditioning task of TBI in allogeneic haematopoietic stem cell transplantation to enable successful engraftment.

INDICATIONSCertain indications: Leukaemias in adults and

childhood: - Acute lymphoblastic leukaemia (ALL), - Acute myeloid leukaemia (AML), - Chronic myeloid leukaemia (CML), - Myelodysplastic syndrome (MDS).Optional indications: Solid tumors in childhood: - Neuroblastomas - Ewing sarcomas - Plasmocytomas / multiple myeloma.In clinical test: - Hodgkin`s disease - Non-Hodgkin`s lymphomas

DOSE USED IN TBI

High Dose TBI – 13.2 Gy in 6 fractions over 3 days

Standard dose TBI – 12 Gy in 6 fractions over 3 days

Low dose TBI – 2 Gy in single fraction

DOSE TO OARS

Lung dose should be restricted to 8 Gy to minimize pneumonitis

HIGH DOSE TBI- DOSE PRESCRIPTION

Disease Dose Fractions Dose Rate Reference

AMLALLCMLLymphomaMM

13.2 Gy 8 # , twice daily

10 cGy/min Dusenbery et al. (Minnesota)

13.5 Gy 6 #, twice daily

3.25cGy/min Blaise et al. (GEGMO)

12 Gy 6 #, twice daily

NR Clift et al. (Seattle)

10-12 Gy 1-8 times/day

3.25cGy/min Devergie et al. (SFGM)

8 Gy 4 # Not mentioned

Moreau et al. (IFM)

LOW DOSE TBI- DOSE PRESCRIPTION

Disease Dose Fractions Dose Rate Reference

AMLCMLLymphomaMDS

2 Gy 1 Fraction 7 cGy/min Hegenbart et al.

5.5 Gy 6 #, twice daily

27.6 – 36.4 cGy/min

Hallemeier et al

4 Gy 1 fraction NR Schmid et al.

2.5 Gy 2 #, twice day

NR Badros et al. (Arkansas)

PRE- REQUISITES FOR TBI

Interdisciplinary approach Radio-oncologists, medical physicists

and haemato-oncologists RT and transplantation must be in

same centre

Conditions with a low risk of infections is recommended

PERFORMANCE OF TBI IN CMC

Positioning Measurements Target volume and Dose ref. points Calculation of MU of target dose Compensator thickness calculation Treatment delivery

POSITION

Patient lies supine Length of patient - not more than 140

cm If length greater than 140 cm – legs

folded with pillow tucked between both legs

Arms flexed and placed near to chestwall

Knees adjoined together, wrapped Positioned at extended SSD of 300 cm

POSITIONING DURING TBI

The patient lying on the side - utilizing opposing beams at large distance(4-6 m).

Measurements

SkullNeck

Shoulder

Chest

Abdomen

Thigh

Knee

Calf

Ankle

TBI AAPM Report No 17

TARGET VOLUME

All malignant cells including those circulating as well as the whole cellular immune system.

The Whole Body, including Skin

Organs with a high risk of recurrence (“homing phenomenon”) and meninges, testes, may require additional local radiotherapy.

TREATMENT PLANNING

AIM – homogenous high dose delivery with sparing the organs at risk

DOSE SPECIFICATION

The total dose to the target volume

Reduced dose to the lungs

The number of fractions and

The lung dose rate.

DOSE REF POINTS

The dose reference point (+) for dose specification to the target volume is

defined at mid abdomen at the height of the

umbilicus according to an international

consensus

DOSE REFERENCE POINTS

D reference, Target

Vol

Lung Ref pt

The dose reference points (∗) for lung dose specification are defined as mid points of both lungs

The lung dose is defined as the mean of the dose at both lung reference points.

Corresponds to the minimum dose to the lungs

PRESCRIPTION OF DOSE AND FRACTIONATION OF TBI

No general recommendation can be given. 12 Gy in 6 fractions – considered standard

PETERS LJ (1980) : The radiobiological bases of TBI. Int J Radiat Oncol Biol Phys 6: 785.

Single fraction TBI - too many complications have been observed.

In fractionated TBI the total dose (DRef) has to be increased by 20-25 % compared to single fraction irradiation.

RADIOBIOLOGY OF TBI

SF2 calculated for leukemia for 7 x 2 Gy regimen

Range of 10 -2 to 10-21

Average case – median of 10-5 clonogenic cells are eliminated – which corresponds to residual disease after good remission

T E Wheldon : Radiobiological basis of TBI. The British Journal of Radiology, 1997

CALCULATION OF MID-PLANE DOSE

Based on umbilical level separation Parallel Opposed lateral Beams

Dose per fraction MU = ___________________

DR at Ext SSD * PDD (Ud)

Does treatment with this MU s alone deliver homogeneous dose to entire body ?

OPTIMIZATION OF DOSE

The homogeneity of dose in the target volume

The effective sparing the lungs

1. DOSE MODIFIERS Influences of irregular body contours

have to be compensated.

For bilateral TBI - a tissue compensators are used in front of and next to head, neck and legs.

TBI AAPM Report 17

CALCULATION OF COMPENSATOR THICKNESS

HVL _________ *

ln Io/I

0.693

Thickness (t) =

I = Io e -mt

2. INCREASING THE DOSE TO PARTS OF THE TARGET VOLUME

For build-up, for higher energy photons : scatter screen (spoiler) has to be positioned close to the patient.

In long term irradiation, remotely positioned dose modifyers are not recommended due to repositioning and increased verification problems

.

3. Dose homogenization in parts of the target volume with reduced dose :

Thoracic wall receives a lower dose due to lung shielding.

Additional irradiation however is not used.

Equivalent homogeneous dose is reduced by only 5% (1-7%), e.g. from 12 Gy TBI dose with 9 Gy lung dose to 11.5 Gy equivalent homogeneous dose – probability of cell kill is not reduced

4. Fluence flattening

Fluence modifying techniques can be used for dose homogenization

E.g. in wide angle collimator or sweeping beam TBI or a wedge filter for oblique incidence of the beam.

SPARING THE LUNGS1. Dose reduction in the lung: To 80% of the prescribed target dose Primary radiation fluence had to reduced by 60-

70 %. Shape and thickness of sheilds must be planned Skin-fixed shieldings are stacks of lead rubber

cut-outs, lead-moulds or stacks of thin lead sheets (for high energy photons, the lead has to be covered by low density material).

2 . Reduction of dose rate: For accelerators: A Lower dose rate

TREATMENT DELIVERY

Delivered in the position which measurements are taken

Under sterile conditions

In vivo dosimetry is done on first day with Semiconductor diodes

OTHER MODALITIES OF TBI

IMMEDIATE TOXICITY

Symptom Single fraction TBI Fractionated TBI

Nausea& Vomiting 45 43

Parotid gland pain 74 6

Xerostomia 58 30

Headache 33 15

Fatigue NR 36

Ocular dryness 16 NR

Esophagitis NR 4

Loss of apetite NR 16

Erythema NR 41

Pruritis NR 4

Diarrhea NR 4

Fever 97 NR

LATE TOXICITY

Salivary glands (22%) – Xerostomia, dental caries, tooth abnormalities

Pneumopathy(10-20%) – Doses greater than 9.4 Gy and single dose TBI increase risk

Cardiac toxicity (2-3%) – Rare, in pts who had anthracycline based chemotherapy

Hepatotoxicity / Venoocculusive disease (70%) – doses greater than 13.2 Gy

Catracts - MC complication. Asso. steroid use and cranial irradiation Kidney Dysfunction - 17% Hypothyroidism – 25 % Growth abnomalities in children Sterility and endocrine abnormalities Secondary MDS or AML ( 1 % at 20 months and 24% at 43 months)

TARGETED TBI – TMI AND TMLI

Total marrow irradiation - skeletal bone. Conditioning regimen for multiple myeloma.

Total marrow and lymphoid irradiation (TMLI) - bone, major lymph node chains, liver, spleen, and sanctuary sites, such as brain.

Conditioning regimen for myeloid and lymphoid leukemias

COLOUR WASH FOR TOMOTHERAPY PLANNED TMI

DVH CURVES FOR TMI

ADVANTAGES OF TMI

Escalate the dose to bone (and containing marrow) up to 20 Gy, while maintaining doses to normal organs at lower levels than in conventional TBI to 12 Gy.

Jeffrey Y. C. Wong et al. Targeted Total Marrow Irradiation Using Three-Dimensional Image-Guided Tomographic Intensity-Modulated Radiation Therapy: An Alternative to Standard Total Body Irradiation, Biology of Blood and Marrow Transplantation 12:306-315 (2006)

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