Does the addition of involved field radiotherapy to high-dose chemotherapy and stem cell transplantation improve outcomes for patients with relapsed/refractory Hodgkin lymphoma?
OBJECTIVE
To evaluate the value of adding involved field radiotherapy (IFRT) to patients with relapsed/refractory Hodgkin lymphoma (HL) undergoing high-dose chemotherapy (HDCT) and stem cell transplantation (SCT).


METHODS
Ninety-two patients with relapsed/refractory HL undergoing HDCT and SCT from 1995 to 2008 were analyzed in a case-control design. Forty-six HL patients treated with IFRT within 2 months of SCT were matched to 46 HL patients who did not receive IFRT based on age, stage at relapse, timing of relapse, histology, and year of SCT. All were evaluated for response, survival, and toxicity with a median followup of 63.5 months.


RESULTS
There was a trend for better disease control in patients receiving IFRT. Specifically, 10/46 IFRT patients (22%) relapsed/progressed after SCT compared with 17/46 control patients (37%). Of the failures after IFRT, 70% were inside the radiation field, all in sites of bulky disease. In patients with nonbulky disease, IFRT also resulted in significantly improved outcomes (failure rate 6% vs. 33%, respectively). When stratified by disease bulk, the use of IFRT was found to significantly improve DFS (p=0.032), but did not affect OS. In addition, IFRT and nonbulky disease were found to be positive prognostic indicators for DFS with hazard ratios of 0.357 (p=0.032) and 0.383 (p=0.034), respectively. Grade IV/V toxicities were significantly higher in the IFRT vs. non-IFRT group (28% vs. 2%; p<0.001), observed only in patients receiving a busulfan-based conditioning regimen.


CONCLUSIONS
Patients with refractory or relapsed HL undergoing HDCT and SCT have a high risk of relapse in sites of prior disease involvement, especially in sites of bulky disease. The use of IFRT is associated with a lower risk of disease progression in these sites; however bulky disease sites are still difficult to control. Toxicity risk is significant, particularly when busulfan-based conditioning is combined with IFRT, and alternative chemotherapy conditioning regimens should be considered.
Kahn
Shannon
S
Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30306, USA. skahn@radonc.emory.org
Flowers
Christopher
C
Xu
Zhiheng
Z
Esiashvili
Natia
N
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002066:Busulfan / Q000008:administration & dosage; D016022:Case-Control Studies; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006689:Hodgkin Disease / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods; D055502:Secondary Prevention; D033581:Stem Cell Transplantation; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult
D005047:Etoposide; D003520:Cyclophosphamide; D002066:Busulfan