Dr. Noelle O Rourke Beatson Oncology Centre, Glasgow RADIOTHERAPY FOR LYMPHOMA???

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1 Dr. Noelle O Rourke Beatson Oncology Centre, Glasgow RADIOTHERAPY FOR LYMPHOMA???

2 History of Radiotherapy 1895 Rontgen describes X-rays 1896 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 onwards Rapid evolution technical XRT

3 A Cure for Hodgkin s Lymphoma from 1950

4 Basic Principles of Radiotherapy Radical doses are intended to cure cancer Higher 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

5 Toxicity of Radiotherapy Acute Toxicity 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 Late Effects Only appear many years after treatment Depend upon repair capacity of irradiated area Not reversible Second malignancies Heart or lung damage

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

7 Late Effects occur with Chemotherapy 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

8 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

9 How Radiotherapy Volumes have changed over the years IFRT, ISRT, INRT

10 SABR shell

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13 Breast Doses vs Lung Doses ARC-A APPA

14 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 NHL 24 Gy for low grade Palliative doses can be very low Good responses possible with just 4Gy Hodgkin s standard dose 30Gy possible to reduce to 20Gy in some

15 Combined Modality in early stage Hodgkin s Cochrane review RCTs, 2564 pats Compared treatment with chemotherapy alone versus treatment with chemo and radiotherapy Significant benefit in survival with radiotherapy 5 yr risk of death 30/1000 vs 15/1000 (9/1000) Significant increase in remission duration

16 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

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19 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

20 Radiotherapy in DLBL US National Cancer Database review 2015 Early stage (I/II) DLBL 59,255 patients Use of RT declined 2000 (47%)-2012(32%) Survival rates with chemo vs chemo/rt 5ys 75% 82% 10ys 55% 64% German study UNFOLDER closed early due to inferior results in arm omitting radiation

21 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

22 Current Guidelines BSH, West of Scotland and NCCN similar: Early stage HL 2-4 ABVD Gy IFRT Advanced HL RT to bulk disease post chemo DLBL stage I/II 3-4RCHOP + 30Gy IFRT Bulky or extranodal disease get RT post chemo

23 Radioimmunotherapy Anti-CD20 Antibody for B cell NHL (Rituximab) Label antibody with Y90 or I131 isotopes which emit radiation hitting the tumour cells = targetted RT Works when patient has become resistant Follicular patients Y90 antibody Rituximab RR 80% 56% CR 30% 16%

24 Radioisotope attached to ritux like antibody 131 I

25 Patient 1 50 year old man, multiply pre-treated follicular NHL Relapse post transplant, kidney failure, no other treatment options Pre-Treatment Bulky abdo disease obstructing kidneys Two weeks post treatment Disease completely resolved Remained in remission 8 years

26 Patient 2 19 year old boy with bulky mediastinal Hodgkin s 6ABVD then CR Relapse one year later: Transplant vs local RT to salvage?

27 Patient 3 85 year old with marginal zone non-hodgkin Lymphoma Large swelling at left eye- eye forced closed and double vision Treated with 4 Gy in 2 fractions in 2 days with immediate response

28 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