Radiotherapy for Lymphoma

The Christie NHS Foundation Trust

Radiotherapy for Lymphoma

Dr Maggie Harris

Consultant Clinical Oncologist

May 2018


Talk Summary

• What is Radiotherapy?

• History of RT in Lymphoma: Past to present

• Important trials

• Current indications for RT in Lymphoma

• New Techniques

• Protons

• Questions?


Historical perspective

• X-rays/isotopes discovered in 1895 (Conrad Roentgen)

• Radium isolated in 1898 (Marie Curie)

• First used for cancer treatment around 100 years ago (Emile Grubbe)

• X-ray tubes developed for treatment

• Development of mega-voltage machines in 1950 (Cobalt-60)

• Linear accelerators

• CT planning

• Multi-leaf collimators

• Intensity modulated radiotherapy

First radiograph 1895Roentgen


How Does Radiotherapy Work?

•Preferentially kills dividing cells

•Can be targeted to include the

tumour and exclude normal tissues


Side Effects.

• Early effects (within days/weeks) depends on total dose of radiotherapy and overall treatment

time :– mucositis

– diarrhoea

– skin erythema

– hair loss

– bone marrow suppression

• Late effects (from 3-6

months onwards) depends on total

dose and fraction size :– skin necrosis, telangectasia, fibrosis,

– bowel strictures and fistulas

– pulmonary fibrosis

– lymphoedema

– cataract formation

– neuropathy (myelitis, plexopathy)

– cardiac damage

– second malignancies

• Note therapeutic index


History of Radiotherapy in

Lymphoma


Historical – Based on Hodgkins

Lymphoma

• Mantle field/Inverted Y (extended field)

• Why changed:

• High local relapse rate (25%) -

• Early and late side-effects

• Chemotherapy


Involved Field


Involved Site Radiotherapy

Gross Tumor

Volume

Usually irregular

in shape and of

variable size

Clinical Target

Volume

Region of

potential disease

Treated Volume

Multi-leaf collimation

Multi-leaf Collimator


Important Trials

• German H10 trial

• RAPID (early stage HL)

• FORT trial – Follicular Lymphoma


German HD 10 study: reducing CMT in early favourable disease

•1370 pts 1998-2003

•Early Favourable disease:

•IA/IIA

•ABVD

•2 cycles •4 cycles

•Involved field RT

•20 Gy •30 Gy

•Engert A et al. N Engl J Med 2010;363:640-652.

•Results equivalent for all 4

arms: 5yr FFTF 92% OS 97%


UK NCRI RAPID TrialPFS in the randomised PET –ve population

(per protocol analysis, n=392)

Per protocol analysis in 392 PET – ve patients

3 year PFS 97.0% IFRT vs 90.7% NFT (p=0.03) in favour of RT

http://www.ncri.org.uk/default.asp


•UK NCRI FoRT•(Follicular Lymphoma Radiotherapy)

•ARM A CONTROL

•24Gy in 12 fractions

•ARM B

EXPERIMENTAL

•4Gy in 2 fractions

•n=299 •n=315


•FORT study : Local Progression Free Interval

•Hazard Ratio: 3.49 (95% CI: 2.06 - 5.90), p<0.001

•2 Year local progression free rate: 93.7% (24Gy) and 80.4% (4Gy)

•Hoskin et al Lancet Oncol. 2014 Apr;15(4):457-

63


How do we decrease late side-

effects of radiotherapy?

• Trials to allow us to omit radiotherapy if not

required

• Better diagnostic scanning – so we know where

to give the radiotherapy to e.g PETCT scans

• Technical advances in radiotherapy to

minimalise radiotherapy field size e.g DIBH (see later)

• Screening/life style changes to prevent late side-

effects


Current Indications for Radiotherapy


Individualised Radiotherapy

Treatment

• Has chemotherapy been given?

• Did they cope with it well? Toxicity?

• What is their chance of being cured already.

• What will radiotherapy add?

• Where is the lymphoma? Site suitable for radiotherapy

• Patient choice

• Importance of late side-effects

• Other possible treatments if relapses


Hodgkin’s indications: Balancing the

risks

• Early stage Hodgkin's Lymphoma

• Advanced Hodgkin's Lymphoma to residual disease

• ?Recurrent localised disease

• Chemo-resistant localised disease


Non-Hodgkin’s Lymphoma

• Early stage localised indolent lymphomas

(follicular, MALT etc)

• Early stage high grade Lymphoma (DLBCL)

after short course chemotherapy.

• To disease left after chemotherapy?

• Advanced Lymphoma that hasn’t responded to

chemotherapy


T cell Lymphoma

• Rarer

• Total skin

electrons


New Techniques…


Deep Inspiratory Breath Hold

(DIBH)Slides courtesy of Guys and St Thomas’s


Deep Inspiratory Breath-hold

• Anatomical changes during inspiration

• Lungs expand

• Chest wall moves upwards and outwards, away

from heart

• Diaphragm moves downwards and flattens

• Heart moves down and back and elongates


FREE

BREATHINGDIBH


Free breathing •DIBH


Christie just about to treat first

lymphoma with DIBH


Proton Therapy

Dr Ed Smith

Clinical Director, Protons

The Christie


The Proton

• Discovered 1917-1919

• Sir Ernest Rutherford (NZ)

• Victoria University, Manchester

• 1835 X weight of an electron

• Charge +1e

• Stable!


Bragg Peak

• Sir William Henry Bragg (UK)

• CambridgeAdelaideLeedsUCL


• Proton Properties

• Protons stop in the patient and we can control this depth

• Minimal exit dose past a tumour being treated

• Reduce Morbidity (OAR and integral dose sparing)

• Photon technologies can produce increasingly conformal plans but increase

integral dose to normal tissues

• A major motivation in most paediatric indications

• Treating radio-resistant tumours close to critical structures

• Dose escalation with an ‘iso-late effect profile’ wrt X Ray Therapy

Increase curative treatment options

• An additional motivation in some adult indications


X Rays

•Ovary

•Ovary

•Pelvis

Bone•Pelvis

Bone

•Bowels

and

Rectum


Protons


X Rays

Lungs

Heart

Liver


Protons


Gantry


Range uncertainty

• The good thing about protons is that they stop in the patient

• The bad thing is that we don’t always know exactly where they stop

→ This is known as ‘Range uncertainty’

Main sources of range uncertainty:

1. CT to proton stopping power

• Not related to patient setup

2. Beam passing through inhomogeneities

• Patient setup, motion, gas/liquid in patient cavities, etc.

3. Patient anatomy changes from planning scan

• Weight loss/gain, tumour regression, etc.


Full UK Service

2021/2

• Two UK High Energy Proton Centres

• Potentially 50+ referring centres

• Up to 1,500 patients / year

UCLH


concrete pile underpinning:

1.2m wide,

each the height of 3 double

decker buses

concrete:

volume equivalent

to eight Olympic

size swimming

pools

cables:

12km of embedded conduits and pipework within the walls

(diameter of the orbital M60 motorway)

building:

weighs more than

10 Eiffel towers

cyclotron:

weight of a Boeing-

747 but size of an

average car


Planned Indications as per 2015

Paediatric Very Young Age

0-16 yo Rhabdomyosarcoma Orbit

Rhabdomyosarcoma Parameningeal/Paraspinal

Rhabdomyosarcoma Pelvis

Ewings

PPNET (extra osseus)

NGGCTs (Germinoma) focal RT

Nasopharyngeal (H&N)

Chordoma/Chondrosarcoma

Osteosarcoma

Adult Type Sarcoma (Bone/ST)

Ependymoma

LGG

Optic Pathway Glioma

Craniopharyngioma

Meningioma (excluding G3)

Esthesioneuroblastoma

Pituitary Adenoma

Salivary Gland Tumours

Juvenile Angiofibroma

Retinoblastoma

Medullo (PNET)

Hodgkins

Selected Neuroblastoma

Selected Wilms Tumour

TYATYA satisfies OP paediatriccriteria

16-24 yo TYA satisfies OP adult criteria

TYA satisfies UK paediatriccriteria

TYA satisfies UK adult criteria

Lymphoma (Selected)

Breast Cancer (Selected)

Ano-Rectal Cancer

Seminoma

Gynae Cancers (Selected)

Adult Chordoma BoS

>24 yo Chondrosarcoma BoS

Para Spinal/Spinal Sarcoma

Meningioma

Orbital/Skull Base NOS

CSI - Curative

Skull base H&N e.g. Paranasal

Overseas

Programme

UK service

expansion


Summary

• Radiotherapy has been used in

Lymphoma for >60 years and is still an

important component of treatment.

• In 2018…

• Radiotherapy is now only given to

selected patients

• Better staging and advances in

radiotherapy planning techniques

has resulted in smaller more

accurate fields and less late side-

effects

Thanks for listening

Any Questions?

Radiotherapy for Lymphoma

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