radiotherapy in lymphoma

1. When should radiotherapy be
used in lymphoma?
Friday, May 24, 2013
Tehran, Iran
Pedram Fadavi MD
Radiation Oncologist, IUMS

2. Roentgen’s laboratory

3. Until 1960s Radiotherapy was the
only non surgical treatment for
lymphoma

4. Current issues in lymphoma
radiotherapy
• Who to treat
• What volume to irradiate
• What dose to use

5. Overview
• Why use radiotherapy to treat lymphomas
• Practicalities of radiotherapy delivery
- Why fractionate
- Treatment planning and delivery
• Indications for external beam radiotherapy
in:
-Hodgkin lymphoma
-Non Hodgkin lymphoma

6. Why use radiotherapy to treat
lymphomas?
• Lymphoma is very radiosensitive
• Relatively small doses of radiotherapy are
required
• Local relapse within an irradiated area is
rare
• Radiotherapy fields are now smaller,
reducing late toxicities

7. Differential effects of irradiation on
tumour and normal tissue

8. Therapeutic Ratio

14. Practicalities of radiotherapy
• Patient must be able to lie still

16. Radiotherapy Planning (1)
• Identify the treatment volume
-Essential to have pre-chemotherapy imaging
- Need up to date diagnostic imaging
- Radiotherapy planning scan
• Treatment volumes
- The visible tumor (GTV)
- Sites of possible microscopic disease (CTV)
- The area to be treated with a margin to allow
for movement and set up accuracy (PTV)

17. Radiotherapy Planning (2)
Considering the best way to deliver the
radiotherapy
• Ensure that PTV receives the intended
treatment dose
• Minimise the dose to normal surrounding
tissues
- Conform fields to treatment volume
- Field arrangements

18. Use of PET to identify the GTV
Terezakis SA, Yahalom J. 2011

19. what is the role for RT as part of
combined-modality treatment in
aggressive lymphoma?

28. RT in indolent lymphomas

30. IFRT remains the treatment of choice of for localized
stage IA and selective stage IIA patients and delivers
long-term disease-free survival and potential cure for
some patients.

31. The conventional dose of curative RT used in
the early studies was considerably larger at
30–40 Gy. However, a British randomized study
demonstrated equivalence of 24 Gy with 40 Gy.

32. Localized LDRT appears to induce apoptosis and this
follicular lymphoma cell death may then elicit a host
immune response mediated by macrophages and
dendritic cells.
This exquisite radiation-induced apoptosis and
subsequent immune response may underlie the
durability of responses seen with both LDRT and
radioimmunotherapy (RIT).

36. What is the role for RT in the modern
management of HL?

38. Identify the risks
GHSG EORTC Stanford
Risk Factors a- Bulky mediastinum a-Bulky mediastinum a-Bulky mediastinum
b-Extranodal disease b- Age >=50 b-Age>=40
ESR>=50 with no
c-ESR>=50 with out B symptoms c-B symptoms c- ESR >=50
Or >=30 with B symptoms Or >=30 with B symptoms
d->=3 nodal sites d->=4 nodal sites D->=3 nodal sites
GHSG EORTC Stanford
Favorable CS I-II CS I-II CS I-II
No risk factors No risk factors No risk factors
Unfavorable CS I- IIA with >=1 CS I- IIA with >=1 CS I- IIA with >=1
risk factor risk factor risk factor
CS IIB with c or d
not a+b (otherwise
advanced)

39. The use of RT also allows a shorter and
safer course of chemotherapy.

40. The combination of reduced chemotherapy
followed by mini-RT has produced disease
control and even overall results that are
significantly superior to those achieved with
chemotherapy alone.

41. .

42. The analysis included five randomized controlled
trials involving 1245 patients. Although the complete
remission rate was similar in the two groups, both
tumour control and OS were significantly better in
patients receiving combined-modality therapy.

43. The authors’ conclusions were that adding RT to
chemotherapy improves tumour control and OS in
patients with early-stage HL.

44. The conclusion from these studies was that after four
cycles of ABVD, 30 Gy is recommended for early-stage
unfavourable Hodgkin lymphoma,whereas 20 Gy is
adequate for early-stage favourable Hodgkin lymphoma
after two cycles ABVD.

47. Involved-site Radiotherapy

48. The principal distinction between involved-node
radiotherapy and involved-site radiotherapy is
that no additional margin around the node
volume is added in involved-node radiotherapy.
Typical margins are as follows:
(a) Head and neck: 0.5-1 cm, depending on local set-up.
(b) Mediastinum: 1 cm transversely and 1.5 cm craniocaudally
(c) All other sites: 1 cm.

49. This is based on defining the site of gross
disease before chemotherapy, the GTV and
using a CT-based volume with an
expansion to form a CTV in the cranio-
caudal direction. The post-chemotherapy
involved nodal chain and residual disease
form the CTV in all other directions.

50. Involved Field(A&B) v Involved Site(C&D)
Radiotherapy
Grinsky, et al 2006

51. Involved field v involved site
radiotherapy
Grinsky, et al 2006

52. Involved site radiotherapy
left neck

53. Involved site radiotherapy
mediastinum

59. Role of RT in Advanced Hodgkin Disease
Offering RT after effective chemotherapy is not standard
practice and is still undergoing investigation.

60. Although a meta-analysis and studies by the GELA
and EORTC groups showed no benefit of
consolidation RT after effective chemotherapy with
suggestions of worsened outcome when RT was
added, more recent data have emerged from 2 large
randomized control trials (RCT) in support of
consolidation RT.

61. .

64. Indications for radiotherapy in
DLBC NHL
• In early stage disease with short course
chemotherapy
• In advanced disease
- Bulky disease at the outset (MINT Study,
Pfreundschuh 2008))
• Risk of relapse increases with size of mass
• Should irradiate masses >10cm at diagnosis
- PET positive at the end of treatment (Sehn et al,
2010)
• Dose 30 Gy in 15 # (Hoskin et al, 2011)

66. Current evidence-based recommendations for radiation doses in
lymphoma are shown below:
Hodgkin lymphoma
1.Early-stage favourable Hodgkin
lymphoma, after two cycles of ABVD,
may be treated with 20 Gy.
2.Early-stage unfavourable, or for
residual or refractory disease in
advanced Hodgkin lymphoma, should
receive 30 Gy.
3.If early-stage unfavourable disease is
treated using BEACOPP rather than
ABVD, the dose may be reduced to
20 Gy.

67. Non-Hodgkin lymphoma
1.Indolent lymphomas (follicular,
marginal zone, small lymphocytic or
chronic lymphocytic lymphoma (CLL)
should be given 24 Gy in 12 fractions.
2.In the palliative setting, follicular
lymphoma patients will respond to 4 Gy
in two fractions.
3.Natural killer cell lymphoma should
receive at least 50 Gy in 25 fractions.
4.All other non-Hodgkin lymphomas
should receive 30 Gy in 15 fractions

68. The planning of radical radiotherapy for lymphoma
patients, both Hodgkin and non-Hodgkin lymphoma,
should be based upon contrast-enhanced 3 mm
contiguous CT imaging with three-dimensional
definition of volumes using the convention of GTV, CTV
and PTV.

69. All patients should be treated with involved-site
radiotherapy unless no pre-chemotherapy
imaging is available,when involved-field
radiotherapy is used.