Audio and slides for this presentation are available on YouTube: http://youtu.be/pkB_mfPtjrA Andrea K. Ng, MD, of Dana-Farber/Brigham and Women's Cancer Center Department of Radiation Oncology, gives an overview of the different types of radiation therapy, the side effects, and how it is used in the treatment of lymphoma. This presentation was given at the 2013 Lymphoma Research Foundation North American Forum on Sept. 29, 2013. http://www.dana-farber.org | http://www.lymphoma.org

1. RADIATION THERAPY IN LYMPHOMA
Andrea K. Ng, MD, MPH
Department of Radiation Oncology
Brigham and Women’s Hospital and Dana-Farber Cancer Institute
Harvard Medical School

2. Questions
 What are types of radiation therapy (RT)?
 When is RT used in the treatment of
lymphoma? What is the evidence?
 What doses of RT are used?
 How have RT technique, field and doses
changed over time for lymphoma?
 What are the side effects of RT?

3. Questions
 What are types of radiation therapy (RT)?
 When is RT used in the treatment of
lymphoma? What is the evidence?
 What doses of RT are used?
 How have RT technique, field and doses
changed over time for lymphoma?
 What are the side effects of RT?

4. Types of RT
 External Beam Radiation Therapy
 Photon beam therapy
 3-D conformal therapy
 Intensity modulated radiation therapy
 Particle beam therapy
 Electron beam therapy
 Proton beam therapy
 Brachytherapy
 Radioactive Isotope

5. Types of RT
 External Beam Radiation Therapy
 Photon beam therapy
 3-D conformal therapy
 Intensity modulated radiation therapy
 Particle beam therapy
 Electron beam therapy
 Proton beam therapy
 Brachytherapy
 Radioactive Isotope

6. Questions
 What are types of radiation therapy (RT)?
 When is RT used in the treatment of
lymphoma? What is the evidence?
 What doses of RT are used?
 How have RT technique, field and doses
changed over time for lymphoma?
 What are the side effects of RT?

7. Indications for RT
 Early stage lymphoma
 disease limited to one side of the diaphragm
 Advanced-stage lymphoma
 disseminated disease, but with sites that are
bulky, extended to bone sites, and/or did not
respond well to chemotherapy

8. RT Alone
 Low-grade lymphoma (or Indolent
lymphoma)
 Follicular lymphoma
 Marginal zone lymphoma or MALT lymphoma
 Nodular lymphocyte predominant Hodgkin
lymphoma (NLPHL)

9. Combined Chemotherapy and RT
 Classical Hodgkin lymphoma
 Intermediate/high-grade lymphoma (or
aggressive lymphoma)
 Diffuse large B-cell lymphoma

10. What is the Evidence?

11. Early-Stage HL: EORTC/GELA H10
3 ABVD + 30Gy INRT
Favorable
If neg : 1 ABVD, no RT
2 ABVD  PET
If pos: 2 eBEACOPP + INRT
2 ABVD  PET
Unfavorable
If neg: 4 ABVD, no RT
4 ABVD + 30Gy INRT
Favorable, PET negative
Unfavorable, PET negative
RT
(n=188)
No RT
(n=193)
HR
RT
(n=251)
No RT
(n=268)
HR
#
events
1
9
9.36
7
16
2.42
1y PFS
100%
94.9%
-
97.3%
94.7%
-

12. Early-Stage HL: EORTC/GELA H10
3 ABVD + 30Gy INRT
Favorable
If neg : 1 ABVD, no RT
2 ABVD  PET
If pos: 2 eBEACOPP + INRT
2 ABVD  PET
Unfavorable
If neg: 4 ABVD, no RT
4 ABVD + 30Gy INRT
Favorable, PET negative
Unfavorable, PET negative
RT
(n=188)
No RT
(n=193)
HR
RT
(n=251)
No RT
(n=268)
HR
#
events
1
9
9.36
7
16
2.42
1y PFS
100%
94.9%
-
97.3%
94.7%
-

13. Early-Stage HL: UK RAPID Trial
IFRT (n=209)
3 ABVD  PET,
if neg
Observation (n=211)
if pos
Intent-to-treat analysis
1 ABVD IFRT (n= 145)
Per protocol analysis
PET neg,
RT
PET neg,
No RT
PET pos,
4th ABVD
+ RT
PET neg,
RT
PET neg,
No RT
PET pos,
4th ABVD+
RT
3 y PFS
93.8%
90.7%
85.6%
97%
90.7%
85.9%
3 y OS
97%
99.5%
93.9%
-
-
-
* Excluded 28 pts who did not get allocated RT and 2 patients allocated to
the observation arm who did get RT

14. Early-Stage HL: UK RAPID Trial
IFRT (n=209)
3 ABVD  PET,
if neg
Observation (n=211)
if pos
Intent-to-treat analysis
1 ABVD IFRT (n= 145)
Per protocol analysis
PET neg,
RT
PET neg,
No RT
PET pos,
4th ABVD
+ RT
PET neg,
RT
PET neg,
No RT
PET pos,
4th ABVD+
RT
3 y PFS
93.8%
90.7%
85.6%
97%
90.7%
85.9%
3 y OS
97%
99.5%
93.9%
-
-
-
* Excluded 28 pts who did not get allocated RT and 2 patients allocated to
the observation arm who did get RT

15. Advanced-Stage HL: GHSG HD15
Stage IIBE, IIBX, III-IV HL
escB x 8
escB x 6
baseline B14 x 8
No further treatment if CR or < 2.5 cm residual mass
If PR with persistent > 2.5 cm mass  PET
RT to 30 Gy to only PET+ pts

16. Advanced-Stage HL: GHSG HD15
Stage IIBE, IIBX, III-IV HL
escB x 8
escB x 6
baseline B14 x 8
No further treatment if CR or < 2.5 cm residual mass
If PR with persistent > 2.5 cm mass  PET
RT to 30 Gy to only PET+ pts
4-year PFS rates of 92.6% (PET -) and 92.1% (PET +)

17. Indolent NHL
Institution
RT Dose
10y-FFR
10y-OS
BNLI
35 Gy
47%
64%
Stanford
35-50 Gy
44%
64%
MDACC
40 Gy
41% (15y)
43% (15y)
PMH
35 Gy
51%
62%
Harvard
36 Gy
46%
75%
BCCA
35 Gy
49%
66%

18. Indolent NHL
Institution
RT Dose
10y-FFR
10y-OS
BNLI
35 Gy
47%
64%
Stanford
35-50 Gy
44%
64%
MDACC
40 Gy
41% (15y)
43% (15y)
PMH
35 Gy
51%
62%
Harvard
36 Gy
46%
75%
BCCA
35 Gy
49%
66%

19. Aggressive NHL: UNFOLDER Trial
 Eligibility: DLBCL, aged 18-60, aa-IPI=1 or
IPI=0 with bulky disease (≥ 7.5 cm)
 Pts with bulky and/or extranodal disease
randomized to 1 of 4 arms:
 Arm I: R-CHOP 21 x 6 alone
 Arm II: R-CHOP 21 x 6; if CR  RT
 Arm III: R-CHOP 14 x 6 alone
 Arm IV: R-CHOP 14 x 6; if CR  RT

20. Aggressive NHL: UNFOLDER Trial
 Eligibility: DLBCL, aged 18-60, aa-IPI=1 or
IPI=0 with bulky disease (≥ 7.5 cm)
 Pts with bulky and/or extranodal disease
randomized to 1 of 4 arms:
 Arm I: R-CHOP 21 x 6 alone
 Arm II: R-CHOP 21 x 6; if CR  RT
 Arm III: R-CHOP 14 x 6 alone
 Arm IV: R-CHOP 14 x 6; if CR  RT

21. UNFOLDER Trial
RT
No RT
3y EFS: 81%
3y EFS: 65%
Held. ICML RT Workshop, 2013

22. UNFOLDER Trial
RT
No RT
Termination
of no RT arm
3y EFS: 81%
3y EFS: 65%
Held. ICML RT Workshop, 2013

23. Questions
 What are types of radiation therapy (RT)?
 When is RT used in the treatment of
lymphoma? What is the evidence?
 What doses of RT are used?
 How have RT technique, field and doses
changed over time for lymphoma?
 What are the side effects of RT?

24. HL: Doses of RT
 Evolved from 40-44 Gy over 4-5 weeks to
now 20-30 Gy over 2-3 weeks
 Candidates for 20 Gy over 2 weeks:
 Low risk, early-stage: only 1-2 sites, < 10 cm, no
B symptoms, normal ESR
 Complete response to chemotherapy

25. NHL: Doses of RT
 Depends on type of lymphoma
 Lower doses for indolent lymphoma
 If given with chemotherapy, depends on
response to chemotherapy
 Lower doses needed if complete response
 From 4 Gy given over 2 days (boom boom),
to > 50 Gy over 5-6 weeks

26. Candidates for “Boom Boom”
• Advanced-stage or recurrent/refractory indolent
lymphoma (follicular lymphoma, marginal zone
lymphoma, mantle cell lymphoma, CLL/SLL, cutaneous
lymphoma) with local symptomatic sites
• May especially benefit patients involvement of sites where
conventional dose RT may have high toxicity (e.g. H&N
sites)
• Not for pts with:
• Localized disease with curative intent
• Disease where durable LC is important (e.g. cord
compression)

27. 2Gy x 2

28. 2Gy x 2

29. Questions
 What are types of radiation therapy (RT)?
 When is RT used in the treatment of
lymphoma? What is the evidence?
 What doses of RT are used?
 How have RT technique, field and doses
changed over time for lymphoma?
 What are the side effects of RT?

30. Evolution of RT in HL
TNI
STNI
IFRT
INRT/ISRT
EVOLUTION OF RT IN HL
2D
40-44 Gy
PET-CT
fusion
Breath-hold
4-D
IMRT
Proton
3D
20-36 Gy

31. Mantle Field
Involved-Site (ISRT)

32. IMRT
Proton Beam RT

33. Free-breathing
PTV
Deep-Inspirational Breath-Hold
(DIBH)
PTV

34. Free-breathing
Heart
DIBH
Heart

35. Free-breathing
DIBH
Lungs
Lungs

36. Questions
 What are types of radiation therapy (RT)?
 When is RT used in the treatment of
lymphoma? What is the evidence?
 What doses of RT are used?
 How have RT technique, field and doses
changed over time for lymphoma?
 What are the side effects of RT?

37. Short-Term Side Effects of RT
 Local skin redness and irritation
 Local temporary hair loss
 Fatigue
 Mouth sores/sore throat/taste changes dry
mouth (head and neck)
 Esophagitis (chest)
 Nausea/vomiting (stomach)
 Diarrhea/cramps (pelvis)

38. Late Effects of RT
 Eye: cataracts, dry eye
 Salivary glands: dry mouth, dental caries
 Thyroid glands: hypothyroidism
 Lungs: lung scarring
 Heart: heart disease
 Ovaries or testes: sterility
 Second malignancy

39. Late Effects of RT
 Eye: cataracts, dry eye
 Salivary glands: dry mouth, dental caries
 Thyroid glands: hypothyroidism
 Lungs: lung scarring
 Heart: heart disease
 Ovaries or testes: sterility
 Second malignancy

40. Reducing Late Effects with
Lower RT Doses

41. Reducing Late Effects with
Smaller Fields

42. Summary
 Multiple recent trials demonstrated
important role of RT as part of lymphoma
therapy
 Doses of RT have decreased over time for
most lymphoma cases
 Modern RT technique allows significant
sparing of normal tissue
 Reduced doses and normal tissue exposure
will limit side effects of RT