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

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

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 …

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

Radiotherapy for FL: Vancouver experience IRRT 1986 - 1998 involved group + ≥ 1 adjacent group INRT≤5cm 1998 - present ≤ 5 cm margin Campbell et al, Cancer 116:3797

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

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

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

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

Use of XRT for early stage FL in the United States: SEER analysis 1973-84 1985-94 1995-04 Pugh et al, Cancer 116:3843

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

National LymphoCare Study: 2004 - 2007

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

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

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

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

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

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.

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

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.

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.

Thank you! Questions?