1. The Christie NHS Foundation Trust Updated June 2010 An Introduction to the nature and management of Lymphoma Radiotherapy in the management of lymphoma Richard Cowan Consultant in Clinical Oncology 13 th October 2010

2. The Christie NHS Foundation Trust Updated June 2010 How to use your Handset Please ensure that your handset is switched on and active

3. The Christie NHS Foundation Trust Updated June 2010 How to use your Handset Use the keypad buttons to select your choice/choices. The keypad supports numeric and alphanumeric

4. The Christie NHS Foundation Trust Updated June 2010 How to use your Handset The Screen will illuminate for a few seconds when voting begins Once you have voted it will say ‘received’ on the screen

5. The Christie NHS Foundation Trust Updated June 2010 Radiotherapy in the management of lymphoma Background to radiotherapy Place of radiotherapy in lymphoma Practical details of radiotherapy Future developments

6. The Christie NHS Foundation Trust Updated June 2010 Wilhelm Conrad Röntgen 1845 - 1923

7. The Christie NHS Foundation Trust Updated June 2010 Discovered X rays 1.1865 2.1875 3.1885 4.1895 5.1905 Q

8. The Christie NHS Foundation Trust Updated June 2010 Discovered X rays 1.1865 2.1875 3.1885 4.1895 ✓ 5.1905 Q

9. The Christie NHS Foundation Trust Updated June 2010 1898

10. The Christie NHS Foundation Trust Updated June 2010 Marie Curie was born in : Q 1.Russia 2.Bulgaria 3.Poland 4.France 5.Bolivia

11. The Christie NHS Foundation Trust Updated June 2010 Marie Curie was born in : Q 1.Russia 2.Bulgaria 3.Poland ✓ 4.France 5.Bolivia

12. The Christie NHS Foundation Trust Updated June 2010 Energy wavelength Electromagnetic spectrum

13. The Christie NHS Foundation Trust Updated June 2010

14. The Christie NHS Foundation Trust Updated June 2010

15. The Christie NHS Foundation Trust Updated June 2010 Until 1960s Radiotherapy was the only non surgical treatment for lymphoma

16. The Christie NHS Foundation Trust Updated June 2010 How effective is Radiotherapy ? Resistant:

17. The Christie NHS Foundation Trust Updated June 2010 How effective is Radiotherapy ? Resistant: –Malignant melanoma

18. The Christie NHS Foundation Trust Updated June 2010 How effective is Radiotherapy ? Resistant: –Sarcomas / melanoma Intermediate:

19. The Christie NHS Foundation Trust Updated June 2010 How effective is Radiotherapy ? Which of these tumours is NOT Intermediate in terms of radiosensitivity: 1.Breast, 2.Testicular seminoma 3.Non small cell lung cancer 4.prostate cancer 5.head and neck cancer Q

20. The Christie NHS Foundation Trust Updated June 2010 How effective is Radiotherapy ? Which of these tumours is NOT Intermediate in terms of radiosensitivity: 1.Breast, 2.Testicular seminoma ✓ 3.Non small cell lung cancer 4.prostate cancer 5.head and neck cancer Q

21. The Christie NHS Foundation Trust Updated June 2010 How effective is Radiotherapy ? Resistant: –Sarcomas / melanoma Intermediate: –Breast, lung, prostate, head and neck cancer

22. The Christie NHS Foundation Trust Updated June 2010 How effective is Radiotherapy ? Resistant: –Sarcomas / melanoma Intermediate: Breast, lung, prostate, head and neck cancer Sensitive: Germ cell tumours Lymphomas

23. The Christie NHS Foundation Trust Updated June 2010 How does Radiotherapy work? Ionising radiation damages cells The most sensitive cellular component is DNA DNA

24. The Christie NHS Foundation Trust Updated June 2010 Radiotherapy – Biological Aspects DNA damage manifests at cell division “Early cell kill” v. “late cell kill” Related to proliferative activity

25. The Christie NHS Foundation Trust Updated June 2010 Radiotherapy – Biological Aspects Early: - usually the cancer –Skin, GI tract, Bone marrow Late: –Kidney, CNS

26. The Christie NHS Foundation Trust Updated June 2010 If the Kidneys receive a toxic dose of radiotherapy how long after radiotherapy will the patient show maximum renal impairment? 1.10 days 2.4 weeks 3.3 months 4.12 months 5.24 months Q

27. The Christie NHS Foundation Trust Updated June 2010 If the Kidneys receive a toxic dose of radiotherapy how long after radiotherapy will the patient show maximum renal impairment? 1.10 days 2.4 weeks 3.3 months 4.12 months ✓ 5.24 months Q

28. The Christie NHS Foundation Trust Updated June 2010 How does Radiotherapy work? The most sensitive cellular component is DNA The malignant cell have impaired DNA repair mechanisms DNA DNA damage can be repaired

29. The Christie NHS Foundation Trust Updated June 2010 Radiotherapy – Biological Selectivity Normal tissue cancer Cell No.

30. The Christie NHS Foundation Trust Updated June 2010 Place of radiotherapy in lymphoma Radiotherapy alone for cure Radiotherapy in combination for cure Palliation

31. The Christie NHS Foundation Trust Updated June 2010 Radiotherapy alone for cure 73 yr old woman who presents with a painless lump in the groin

32. The Christie NHS Foundation Trust Updated June 2010 Radiotherapy alone for cure 73 yr old woman who presents with a painless lump in the groin Biopsy : Follicular lymphoma

33. The Christie NHS Foundation Trust Updated June 2010 Radiotherapy alone for cure 73 yr old woman who presents with a painless lump in the groin Biopsy : Follicular lymphoma stage IA

34. The Christie NHS Foundation Trust Updated June 2010 Radiotherapy alone for cure 73 yr old woman who presents with a painless lump in the groin Biopsy : Follicular lymphoma stage IA FORT Study : 24Gy in 12 # compared with 4Gy in 2#

35. The Christie NHS Foundation Trust Updated June 2010 How effective is Radiotherapy ? Intermediate: –prostate cancer 70Gy Sensitive : follicular lymphoma24Gy (4Gy)

36. The Christie NHS Foundation Trust Updated June 2010 Radiotherapy alone for cure 73 yr old woman who presents with a painless lump in the groin Biopsy : Follicular lymphoma stage IA 24 Gy Radiotherapy 3 months later the chance of complete remission Q 1.25% - 35% 2.40% - 50% 3.55% - 65% 4.65% - 75% 5.85% - 95%

37. The Christie NHS Foundation Trust Updated June 2010 Radiotherapy alone for cure 73 yr old woman who presents with a painless lump in the groin Biopsy : Follicular lymphoma stage IA 24 Gy Radiotherapy 3 months later the chance of complete remission Q 1.25% - 35% 2.40% - 50% 3.55% - 65% 4.65% - 75% 5.85% - 95% ✓

38. The Christie NHS Foundation Trust Updated June 2010 Radiotherapy alone for cure 33 year old woman

39. The Christie NHS Foundation Trust Updated June 2010 Radiotherapy alone for cure 33 year old woman Biopsy : Hodgkins lymphoma Stage I A (nodular lymphocyte predominant)

40. The Christie NHS Foundation Trust Updated June 2010 Radiotherapy alone for cure 33 year old woman Biopsy : Hodgkins lymphoma Stage I A (nodular lymphocyte predominant) 30Gy in 15# (3 weeks)

41. The Christie NHS Foundation Trust Updated June 2010 How effective is Radiotherapy ? Intermediate: –prostate cancer 70Gy Sensitive : –follicular lymphoma24Gy (4Gy) –Hodgkins lymphoma 30Gy

42. The Christie NHS Foundation Trust Updated June 2010 Radiotherapy in combination 32 year old man With a cough and weight loss Hodgkins stage III B

43. The Christie NHS Foundation Trust Updated June 2010 Radiotherapy in combination 32 year old man With a cough and weight loss Hodgkins stage III B After 6 cycles of ABVD

44. The Christie NHS Foundation Trust Updated June 2010 Following 6 cycles of ABVD

45. The Christie NHS Foundation Trust Updated June 2010 Following 6 cycles of ABVD

46. The Christie NHS Foundation Trust Updated June 2010 The practicalities of radiotherapy

47. The Christie NHS Foundation Trust Updated June 2010 Dose and duration of treatment “Low Dose “ (30 Gy rather than 70Gy) Curative : 15 treatments of 2 Gy = 3 weeks Shorter treatments : Palliative Radiotherapy

48. The Christie NHS Foundation Trust Updated June 2010 Dose and duration of treatment summary Curative : –Hodgkins 30Gy in 3 weeks (15#) –DLBC30 Gy in 3 weeks –Follicular 24Gy in 2 weeks Palliative 1 – 10 #

49. The Christie NHS Foundation Trust Updated June 2010 The practicalities of radiotherapy

50. The Christie NHS Foundation Trust Updated June 2010

51. The Christie NHS Foundation Trust Updated June 2010 Low energy X-rays e.g. 100KV Electrons

52. The Christie NHS Foundation Trust Updated June 2010 High energy x-rays e.g. 6Mev

53. The Christie NHS Foundation Trust Updated June 2010

54. The Christie NHS Foundation Trust Updated June 2010 PET CT

55. The Christie NHS Foundation Trust Updated June 2010

56. The Christie NHS Foundation Trust Updated June 2010 Side effects of radiotherapy Acute : - Acute inflammation : –Red skin –Mucositis –Bowel upset –Alopecia Tiredness

57. The Christie NHS Foundation Trust Updated June 2010 Side effects of radiotherapy Acute side effects : - Q 1.Start on the first day of treatment and last for the duration of the treatment 2.Start towards the end of the treatment and last for 3 – 4 weeks 3.Start on the first day of treatment and last for 3 – 4 weeks post treatment 4.Start towards the end of treatment and last for 3 – 4 months post treatment

58. The Christie NHS Foundation Trust Updated June 2010 Side effects of radiotherapy Acute side effects : - Q 1.Start on the first day of treatment and last for the duration of the treatment 2.Start towards the end of the treatment and last for 3 – 4 weeks ✓ 3.Start on the first day of treatment and last for 3 – 4 weeks post treatment 4.Start towards the end of treatment and last for 3 – 4 months post treatment

59. The Christie NHS Foundation Trust Updated June 2010 Side effects of radiotherapy late : - 6 months and beyond : chronic inflammation : –Lung (visible on CXR) –Bowel –Salivary glands –endocrine 2 nd malignancy cardiac

60. The Christie NHS Foundation Trust Updated June 2010 Side effects of radiotherapy Depend upon : Dose

61. The Christie NHS Foundation Trust Updated June 2010 Side effects of radiotherapy Depend upon : Dose (good for lymphoma)

62. The Christie NHS Foundation Trust Updated June 2010 Side effects of radiotherapy Depend upon : Dose (good for lymphoma) Volume irradiated

63. The Christie NHS Foundation Trust Updated June 2010 Side effects of radiotherapy Depend upon : Dose (good for lymphoma) Volume irradiated (small is beautiful)

64. The Christie NHS Foundation Trust Updated June 2010 90 Y Zevalin Zevalin(Ibritumomab) –Anti-CD20 murine parent of rituximab Tiuxetan –Chelator, conjugated to antibody forming strong urea-type bond –Stable retention of 90 Y Yttrium-90 –t 1/2 = 64 hours –Outpatient administration –Beta emission - 5mm 90 Y radionuclide Tiuxetan Zevalin

65. The Christie NHS Foundation Trust Updated June 2010 Future developments Technical advances : Imaging Delivery –Intensity Modulated Radiotherapy (IMRT) –Image Guided Radiotherapy (IGRT)

66. The Christie NHS Foundation Trust Updated June 2010 Future developments New molecules : –Increase tumour sensitivity –Protect normal tissues

67. The Christie NHS Foundation Trust Updated June 2010 What is for lunch ? 1.A Big Mac 2.Thai Chicken kebabs 3.Bacon butties 4.Salmon and Champagne Q