1. Radiotherapy L
R di th Lymphomas
h
Mary Gospodarowicz MD
Princess Margaret Hospital
University of Toronto, Toronto, Canada

2. Changing Landscape in Lymphoma
• 90% of cases in adults
• median age - 64 yrs
• 2008 Statistics
US Canada
• 66 120 new cases 7 000
• 19 160 deaths 3 100
• @ 500 000 people living with lymphoma
• 90% B-cell
B-
• @ 40% DLBCL
• 10% T-cell
T-

3. RT in Non-Hodgkin L mphoma
Non- Lymphoma
• Challenges
– Only 4 - 6% of all cancers
– Numerous distinct disease entities
• Mycosis fungoides
• Primary brain lymphoma
y yp
• Gastric MALT
• Burkitt’s
– Changing outcomes
– Little level 1 evidence to guide practice

4. Radiation Therapy in Cancer
• Local therapy
– Proven most effective agent in
providing l
idi local t
l tumour control
tl
– Proven capable of curing localized
disease in most cancers
– Compensates for diagnostic ambiguity
p g gy
• ‘histology agnostic’
– Few contraindications

5. Radiation Therapy in Cancer
• Local therapy
• Proven most effective agent in providing
local tumour control
• Proven capable of curing localized disease
in most cancers
• Compensates for diagnostic ambiguity
• ‘histology agnostic’
histology agnostic
• Few contraindications

6. RT in Lymphomas
L mphomas
• Objective of RT
Obj ti f
– Almost always to achieve local control
• Outcomes of interest
– Pattern of failure
• Local control
• Overall failure rate
– Survival
– Toxicity

7. Stage I&II Follicular Lymphoma 1967-99
1967-
Stage I-II
I- - 668 pts
• Stage I-II RT alone
I- - 460 pts
– median follow-up
ed a follow-
oo - 12.5 y s
5 yrs
• range - up to 32 yrs
• Treatment – IF RT 30-35 Gy
30-
• Relapse
• distant - 89 %
• distant + local - 6%
• isolated local relapse - 5%

8. PMH 1968 – 1999
Stage I-II Follicular Lymphoma RT Alone
I-
460 patients

9. PMH 1968 – 1999
Stage I-II Follicular L
St I- F lli l Lymphoma RT Al
h Alone
No relapse
80
Relapse
70
60
Age
50
40
30
20
0 5 10 15 20 25 30 35
Time to relapse or f ll
Ti l follow-up

10. Stage I-II MZL PMH 1989-2004
MALT 1989 - 2004
• 166 pts treated with RT
t t t d ith
• median follow-up 7.6 yrs (0.6 – 16.2)
follow-
• median age 60 yrs (23-93)
(23-
• F:M=2:1
• stage I 148 (89%)
• stage II
t 18 (11%)

11. Stage I-II MZL PMH 1989-2004
Presenting Sites
Orbit and adnexa 70 (42%) Skin & soft tissues 4
Salivary gland 28 (17%) Breast 4
Stomach
St h 22 (13%) Rectum
Rt 1
Thyroid 21 (13%) Meninges 1
Other head & neck* 6
neck Thymus 1
Lung 4
Bladder 4
*nasopharynx - 3, maxillary sinus - 1
larynx - 1, Hypopharynx - 1

12. Stage I/II MALT lymphoma - Relapse
g yp p
Stomach/Thyroid (n=43) Relapse
2 yrs: 13/31 (52%)
5 yrs: 25/31 (81%)
Other sites (n=123)
> 5 yrs: 6/31 (19%)
y ( )
10-year RFR
Thyroid 95%
Stomach 100%
Salivary gland 68%
Orbit 67%

13. Stage I/IIE MALT lymphoma - Survival
--- 10 yr CSS - 98%
— 10 yr OS - 87%
…. 10 yr RFR 77%
RFR-

14. Limited- g mantle-
Limited-stage mantle-cell lymphoma
yp
Leitch et al Annals of Oncology 14: 1555 1561 2003
al. 1555–1561,

15. Int J Radiat Oncol Biol Phys 65: 1185 91 2006
1185–91,

16. Localized DLBCL
Heterogeneous disease
Phenotypic, molecular characteristics
Nodal vs. extranodal presentations
vs
Stage I vs. II (II localized vs.. extensive)
B-symptoms
LDH
Age d
A and performance status
f tt
Comorbidity

17. Spectrum of Localized DLBL

18. PMH Experience 1984 -2003
600 patients with stage I-II
I-
Age 15 - 91 median - 57 yrs
Follow-
Follow-up 0.4 – 22 yrs
y median - 10.1 yrs
y
Stage I - 317 B-symptoms - 64
Stage II - 283
g Extranodal - 354
Chemo 3/4 courses - 233
Chemo 5/6 courses - 336
median RT dose – 35 Gy
pre-
pre-rituximab

19. Overall Survival
PMH DLBCL – CMT 1984-2003
1984-

20. Survival by age
PMH DLBCL – CMT 1984-2003
1984-

21. Probability of Local Relapse
PMH DLBCL – CMT 1984-2003
1984-

22. CHOP non-responders
non- p
Probability of Death from Lymphoma
PMH DLBCL – CMT 1984-2003
1984-

23. Rituximab Era
Rituximab
Rit i b gradually i t d
d ll introduced t th
d to the
management of all DLBCL
Outcomes improved
Role of RT questioned
q
No level 1 evidence
For the benefit of RT
For the lack of benefit of RT

25. Practice
Guidelines
G id li

26. T/NK-
T/NK-cell Nasal Lymphoma
Note: Non-randomized comparison
Non randomized
RT n=18
CMT n=61
Cheung et al, IJRBOP 2002; 54: 182-90

27. IELSG Testis Lymphoma
Kaplan-Meier survival estimates
1.00
Actuarial risk of contralateral testicular failure
by prophylactic scrotal RT
(log
(l rank t t p=0.0027)
k test, 0 0027)
0.75
No scrotal XRT
0.50
0 50
0.25
Prophylactic XRT
0.00
0 10 20 30
PFS

28. RT - Refractory-Recurrent DLBCL
Refractory-
Martens et al, IJROBP 64: 1183-7, 2006
1183-

29. Int J Radiat Oncol Biol Phys, 51:148–155, 2001

30. Austral Radiol 50:222–7, 2006

32. RO Practice in Lymphomas
• Change in radiation oncology p
g gy practice
– Target volume rather than nodal region
treated
– GTV, CTB, PTV defined and treated
– Most practice in adjuvant setting
• N GTV CTV non-standard
No GTV, non- dd
– Need to monitor and report RT relevant
outcomes
• Local control
• Patterns of relapse

33. RT Planning
Requires optimal
R i ti l
pre-chemotherapy
imaging

34. Current Standard
• Target - post chemotherapy CTV
• Dose and fractionation
– 30 – 35 Gy in 15-20 fractions
15-
• 3D CRT / IMRT
– protect normal tissues
• CT planning
• Image guidance as required

36. Role of RT
All trials show improved local control
Very safe treatment
Minimal acute and late severe toxicity
Modern techniques – lower acute toxicity
Best local therapy cannot improve
distant disease control
If systemic therapy results in 100% local
control – no need for RT

37. Current contro ersies
C rrent controversies
•L
Localized f lli l l
li d follicular lymphoma
h
– Curable with RT or just very slow natural
history
hi t
• MALT
– Role of RT in rare presentations
– Need to learn more about the natural
history

38. Current contro ersies
C rrent controversies
• Localized DLBCL
L li d
– Is RT needed in R-CHOP era
R-
• Does it add to the chemotherapy
– Must conduct studies that include optimal
chemotherapy and ask RT question
• Extranodal lymphomas
– Differences btwn EN and N presentations

39. Current contro ersies
C rrent controversies
• R l of RT i FDG PET era
Role f in
– Assessment of response to chemotherapy
using mid-treatment FDG PET
i mid-t t
id t
– Post chemotherapy PET assessed
response as selection factor for RT
• Role of RT in PET +ve and PET –ve cases
• Patterns of failures in above situations

40. Future
• Biologic imaging
g gg
• Disease extent
• Response
p
• Selection for adjuvant treatment
• Role of precision RT
• Molecular disease characteristics
• D fi iti of di
Definition f disease entities
titi
• Impact on the management