RADIATION THERAPY IN LYMPHOMA

Andrea K. Ng, MD, MPH
Department of Radiation Oncology
Brigham and Women’s Hospital and Dan...
Questions
 What are types of radiation therapy (RT)?
 When is RT used in the treatment of

lymphoma? What is the evidenc...
Questions
 What are types of radiation therapy (RT)?
 When is RT used in the treatment of

lymphoma? What is the evidenc...
Types of RT
 External Beam Radiation Therapy
 Photon beam therapy
 3-D conformal therapy
 Intensity modulated radiatio...
Types of RT
 External Beam Radiation Therapy
 Photon beam therapy
 3-D conformal therapy
 Intensity modulated radiatio...
Questions
 What are types of radiation therapy (RT)?
 When is RT used in the treatment of

lymphoma? What is the evidenc...
Indications for RT
 Early stage lymphoma
 disease limited to one side of the diaphragm

 Advanced-stage lymphoma
 diss...
RT Alone
 Low-grade lymphoma (or Indolent

lymphoma)
 Follicular lymphoma
 Marginal zone lymphoma or MALT lymphoma

 N...
Combined Chemotherapy and RT
 Classical Hodgkin lymphoma
 Intermediate/high-grade lymphoma (or

aggressive lymphoma)
 D...
What is the Evidence?
Early-Stage HL: EORTC/GELA H10
3 ABVD + 30Gy INRT

Favorable

If neg : 1 ABVD, no RT
2 ABVD  PET
If pos: 2 eBEACOPP + INR...
Early-Stage HL: EORTC/GELA H10
3 ABVD + 30Gy INRT

Favorable

If neg : 1 ABVD, no RT
2 ABVD  PET
If pos: 2 eBEACOPP + INR...
Early-Stage HL: UK RAPID Trial
IFRT (n=209)
3 ABVD  PET,

if neg

Observation (n=211)
if pos
Intent-to-treat analysis

1 ...
Early-Stage HL: UK RAPID Trial
IFRT (n=209)
3 ABVD  PET,

if neg

Observation (n=211)
if pos
Intent-to-treat analysis

1 ...
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...
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...
Indolent NHL
Institution

RT Dose

10y-FFR

10y-OS

BNLI

35 Gy

47%

64%

Stanford

35-50 Gy

44%

64%

MDACC

40 Gy

41%...
Indolent NHL
Institution

RT Dose

10y-FFR

10y-OS

BNLI

35 Gy

47%

64%

Stanford

35-50 Gy

44%

64%

MDACC

40 Gy

41%...
Aggressive NHL: UNFOLDER Trial
 Eligibility: DLBCL, aged 18-60, aa-IPI=1 or

IPI=0 with bulky disease (≥ 7.5 cm)
 Pts wi...
Aggressive NHL: UNFOLDER Trial
 Eligibility: DLBCL, aged 18-60, aa-IPI=1 or

IPI=0 with bulky disease (≥ 7.5 cm)
 Pts wi...
UNFOLDER Trial
RT
No RT

3y EFS: 81%
3y EFS: 65%

Held. ICML RT Workshop, 2013
UNFOLDER Trial
RT
No RT

Termination
of no RT arm

3y EFS: 81%
3y EFS: 65%

Held. ICML RT Workshop, 2013
Questions
 What are types of radiation therapy (RT)?
 When is RT used in the treatment of

lymphoma? What is the evidenc...
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...
NHL: Doses of RT
 Depends on type of lymphoma
 Lower doses for indolent lymphoma

 If given with chemotherapy, depends ...
Candidates for “Boom Boom”
• Advanced-stage or recurrent/refractory indolent
lymphoma (follicular lymphoma, marginal zone
...
2Gy x 2
2Gy x 2
Questions
 What are types of radiation therapy (RT)?
 When is RT used in the treatment of

lymphoma? What is the evidenc...
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
...
Mantle Field

Involved-Site (ISRT)
IMRT

Proton Beam RT
Free-breathing

PTV

Deep-Inspirational Breath-Hold
(DIBH)

PTV
Free-breathing

Heart

DIBH

Heart
Free-breathing

DIBH

Lungs
Lungs
Questions
 What are types of radiation therapy (RT)?
 When is RT used in the treatment of

lymphoma? What is the evidenc...
Short-Term Side Effects of RT
 Local skin redness and irritation
 Local temporary hair loss

 Fatigue
 Mouth sores/sor...
Late Effects of RT
 Eye: cataracts, dry eye
 Salivary glands: dry mouth, dental caries

 Thyroid glands: hypothyroidism...
Late Effects of RT
 Eye: cataracts, dry eye
 Salivary glands: dry mouth, dental caries

 Thyroid glands: hypothyroidism...
Reducing Late Effects with
Lower RT Doses
Reducing Late Effects with
Smaller Fields
Summary
 Multiple recent trials demonstrated

important role of RT as part of lymphoma
therapy
 Doses of RT have decreas...
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How Radiation Therapy Is Used in the Treatment of Lymphoma

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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

Published in: Health & Medicine, Technology

Transcript of "How Radiation Therapy Is Used in the Treatment of Lymphoma "

  1. 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. 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. 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. 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. 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. 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. 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. 8. RT Alone  Low-grade lymphoma (or Indolent lymphoma)  Follicular lymphoma  Marginal zone lymphoma or MALT lymphoma  Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)
  9. 9. Combined Chemotherapy and RT  Classical Hodgkin lymphoma  Intermediate/high-grade lymphoma (or aggressive lymphoma)  Diffuse large B-cell lymphoma
  10. 10. What is the Evidence?
  11. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 21. UNFOLDER Trial RT No RT 3y EFS: 81% 3y EFS: 65% Held. ICML RT Workshop, 2013
  22. 22. UNFOLDER Trial RT No RT Termination of no RT arm 3y EFS: 81% 3y EFS: 65% Held. ICML RT Workshop, 2013
  23. 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. 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. 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. 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. 27. 2Gy x 2
  28. 28. 2Gy x 2
  29. 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. 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. 31. Mantle Field Involved-Site (ISRT)
  32. 32. IMRT Proton Beam RT
  33. 33. Free-breathing PTV Deep-Inspirational Breath-Hold (DIBH) PTV
  34. 34. Free-breathing Heart DIBH Heart
  35. 35. Free-breathing DIBH Lungs Lungs
  36. 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. 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. 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. 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. 40. Reducing Late Effects with Lower RT Doses
  41. 41. Reducing Late Effects with Smaller Fields
  42. 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

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