1. Role for XRT in treatment of early stage Follicular lymphoma?
Jonathan W. Friedberg M.D., M.M.Sc.
University of Rochester Medical Center

2. Background: Stage 1 Follicular lymphoma
30% of newly diagnosed FL patients are Stage 1/2
Guidelines recommend XRT as first line therapy
Single institution, retrospective studies suggest prolonged PFS in a proportion of patients, with few events after 10 years of follow-up.
No randomized studies have been performed.
SEER analysis suggests only one-third of patients with early stage FL are treated with XRT in the United States
Pugh et al, Cancer 116: 3843

3. UpToDate Follicular Lymphoma 2013:
For most patients with stage I or nonbulky stage II FL, we suggest initial treatment with radiation therapy rather than treatment with chemotherapy or an initial period of observation …

4. Early Stage Follicular Lymphoma: outcomes with RT alone
Institution
Author (year)
# of pts.
10 yr
FFR OS
DSS
BNLI
Vaughn Hudson
(1994)
208
47%
64%
70%
Royal Marsden
Pedlebury
(1995) 58
43%
79% NA
Stanford
MacManus
(1996)
177
44%
PMH
Petersen
(2004)
460
51%
62%
SEER
Pugh
(2009)
2222

5. Radiotherapy for FL: Vancouver experience
IRRT
involved group + ≥ 1 adjacent group
INRT≤5cm
present
≤ 5 cm margin
Campbell et al, Cancer 116:3797

6. Overall survival (OS):
Early stage FL with XRT
85%
66%
46%

7. PFS by RT field size
INRT≤ 5cm
IRRT
P = 0.498

8. Time to transformation: Early stage FL pts treated with XRT
Bains et al, Ann Oncol 24:428

9. SEER- FL stage I-II (6568 pts): NHL-specific survival: Initial Tx
Pugh et al, Cancer 116:3843

10. Use of XRT for early stage FL in the United States: SEER analysis
Pugh et al, Cancer 116:3843

11. Follicular lymphoma Stage I/II No initial treatment: Stanford experience
43 patients (11 Stage 1) managed with no initial treatment
At median follow-up of 86 months, 27 patients (63%) had not required treatment.
Survival equivalent to immediate therapy with XRT.
“We consider no initial therapy to be an acceptable option for selected patients”
PFS: Stage I/II FL
No initial treatment
Advani et al, JCO 22:1454

12. National LymphoCare Study: 2004 - 2007

13. Identification of Rigorously-Staged Follicular Lymphoma Stage 1 Patients
Work-up included (CT or PET) and bone marrow
N=206
Work-up included PET and bone marrow
N=128
No bone marrow/No imaging: 61
Imaging only: 180
Bone marrow only: 20

14. Identification of Rigorously-Staged Follicular Lymphoma Stage 1 Patients
Work-up included (CT or PET) and bone marrow
N=206
Work-up included PET and bone marrow
N=128
No difference in outcome
No clear benefit to PET

15. Initial Treatment of Stage 1 FL: National LymphoCare Study
Friedberg et al, JCO 27:1202

16. Baseline Characteristics by Initial Treatment (% of pts)
XRT
N=56
Obs
N=35
Ritux
N=25
R-chemo
N=57
Chemo
N=26 p
Age >60 55 65 56 44 46
0.3
Hb <12 g/dL 9 14 16 19 13
0.7
LDH Elevated 7 27
0.19
Grade III 8 57
<0.01
B-sx - Yes 5 3 20 12 23
0.03

17. Progression-free Survival: rigorously staged stage 1 FL patients
Friedberg et al, JCO 30:3368

18. Conclusions: Stage 1 Follicular lymphoma
Complete staging with bone marrow biopsy and CT imaging allows accurate prediction of Stage I outcome in FL. There is no added prognostic benefit to staging with PET.
Excellent outcome is observed with over 5 years of follow-up with various treatment modalities. Observation, rituximab, R-Chemo and combined modality approaches are reasonable and effective options, in addition to XRT.
Our data questions whether XRT is best choice and whether it has any impact on outcome in this group of patients.

19. My approach: Stage 1 Follicular lymphoma
Always perform complete staging, including bone marrow biposy.

20. My approach: Stage 1 Follicular lymphoma
Always perform complete staging, including bone marrow biposy.
XRT alone remains my primary therapy. However, if toxicity is a concern due to location of disease or patient choice, I generally recommend watch and wait.

21. My approach: Stage 1 Follicular lymphoma
Always perform complete staging, including bone marrow biposy.
XRT alone remains my primary therapy. However, if toxicity is a concern due to location of disease or patient choice, I generally recommend watch and wait.
I treat early stage grade III disease with combined modality therapy like early stage DLBCL in most patients. In this group, I consider rituximab maintenance.

22. Thank you!
Questions?