RADIOTHERAPYFOR LYMPHOMA ???

Dr. Noelle O’RourkeBeatson Oncology Centre, Glasgow

History of Radiotherapy

1895 Rontgen describes X-rays1896 Becquerel radioactivity

1905 Radiation is used to treat tumours

1950 Radiotherapy to cure Hodgkin’s Lymphoma

1970s Chemotherapy, CT scans

1980s onwards Late Effects

2000 onwardsRapid evolution technical XRT

A Cure for Hodgkin’s Lymphoma from 1950

Basic Principles of Radiotherapy

‘Radical’ doses are intended to cure cancerHigher dose spread out a little each day over several weeks

‘Palliative’ doses are lower dose intended to shrink tumours and improve symptoms – often given as a single dose or spread out over a few days

The higher ‘radical’ doses require complex computerised treatment plans whereas palliative treatments usually simpler set-up and can start at once

Toxicity of Radiotherapy

‘Acute’ Toxicity ‘Late’ Effects

Immediate side effects

Depends on which part of the body is being treated

Fatigue

Skin redness

Sore swallowing if chest RT

These effects self repair within weeks of finishing treatment

Only appear many years after treatment

Depend upon repair capacity of irradiated area

Not reversible

Second malignancies

Heart or lung damage

Risk of late onset breast cancer varies with age at time of RT

Late Effects occur withChemotherapy and Radiotherapy Late cardiac and pulmonary toxicity, with chemo

and with RT

Solid tumours – breast and lung – secondary to RT

Hypothyroidism- neck RT

Gonadal and leukaemia risk only associated with chemo

Increased radiation damage late effects if: dose>40Gy, fraction per day >3Gy, ant weighting of beams, orthovoltage energy, -NONE of these are used in modern radiotherapy

RT vs Chemo vs Combination

Radiotherapy alone was used to treat lymphomas 1950s-1970s

Alkylating agents and wider use of chemo from 1970s, introduced in advanced stages of disease first

As late effects of large field RT became obvious a change towards more chemo and omitting RT

Current practice refining best balance of combining the two modalities

How Radiotherapy Volumes have changed over the years

IFRT, ISRT, INRT

SABR shell

a b

1

3

2

4

ARC-A APPA

Breast Doses vs Lung Doses

What dose of Radiation?

Radiotherapy dose is measured in Grays ‘Solid’ cancers need 65-70Gy to kill tumour

BNLI trial: 30 Gy for high grade NHL24 Gy for low grade

‘Palliative’ doses can be very lowGood responses possible with just 4Gy

Hodgkin’s standard dose 30Gypossible to reduce to 20Gy in some

Combined Modality in early stage Hodgkin’s

Cochrane review 2017 7RCTs, 2564 pats

Compared treatment with chemotherapy alone versus treatment with chemo and radiotherapy

Significant benefit in survival with radiotherapy5 yr risk of death 30/1000 vs 15/1000 (9/1000)

Significant increase in remission duration

RAPID clinical trial UK

If your PET scan is negative you are put into one of 2 groups at random

Trial seeking to omit radiotherapy in good risk patients

Indications for radiotherapy in Hodgkin’s Lymphoma

Primary treatment stage IA Lymphocyte predominant

Combined modality treatment of early stage

Consolidation of bulk disease/resid PET+Converting PR into CR

Palliation of advanced disease

Radiotherapy in DLBL

US National Cancer Database review 2015Early stage (I/II) DLBL 59,255 patientsUse of RT declined 2000 (47%)-2012(32%)

Survival rates with chemo vs chemo/RT5ys 75% 82%

10ys 55% 64%

German study UNFOLDER closed early due to inferior results in arm omitting radiation

Indications for radiotherapy in Non-Hodgkin’s Lymphoma

Combined modality treatment of stage I/II disease

Consolidation treatment for bulk disease

Primary treatment for local disease:– follicular, MALT and poor PS HG

Palliation of advanced disease

TBI transplant conditioning

Radioimmunotherapy of B cell NHL

Current Guidelines

BSH, West of Scotland and NCCN similar:

Early stage HL 2-4 ABVD+ 20-30Gy IFRT

Advanced HL RT to bulk disease post chemo

DLBL stage I/II 3-4RCHOP + 30Gy IFRTBulky or extranodal disease get RT post chemo

Radioimmunotherapy

Anti-CD20 Antibody for B cell NHL (Rituximab)

Label antibody with Y90 or I131 – isotopes which emit radiation hitting the tumour cells = targettedRT

Works when patient has become resistant

Follicular patientsY90 antibody Rituximab

RR 80% 56%

CR 30% 16%

131I

Radioisotope attached to ritux like antibody

Patient 150 year old man, multiply pre-treated follicular NHLRelapse post transplant, kidney failure, no other treatment options

Pre-TreatmentBulky abdo disease obstructing kidneys

Two weeks post treatmentDisease completely resolvedRemained in remission 8 years

Patient 219 year old boy with bulky mediastinal Hodgkin’s 6ABVD then CRRelapse one year later: Transplant vs local RT to salvage ?

Patient 385 year old with marginal zone non-Hodgkin LymphomaLarge swelling at left eye- eye forced closed and double visionTreated with 4 Gy in 2 fractions in 2 days with immediate response

The Future Defining optimal use of Combined modality

therapy : how much chemo and how much radiation and how best to combine ?

Utilising RT technology to maximise tumour kill while protecting normal tissues

Incorporating radioimmunotherapy into standard therapy for B cell NHL

Combining radiation with immunotherapy

‘Personalising’ treatment on basis of pathology, distribution of disease, response to initial treatment and individual risks