Preasct Cytoreductive Radiation Therapy

One of the main advantages of using RT as a part of cytoreductive therapy is maximizing response prior to HDT/ASCT, which, some groups have reported, is associated with a better outcome.17 It also eliminates any delay in RT administration, a modality that increasingly has been left out of front-line therapy for HL. In addition, hematologic toxicity secondary to RT in the post-ASCT setting is of little clinical importance when administered pre-ASCT. Conversely it contributes to mucositis and pneumonitis, particularly if mediastinal radiation is administered.

A Stanford series by Poen et al. included 100 consecutive patients of which 24 received IFRT, 18 as part of cytoreductive therapy and six in consolidative setting. In the 39 radiation-naive patients in this study, IFRT improved OS (93% vs 55%, P = 0.02) with a trend toward improved FFTF. For the group as a whole, FFTF and OS did not improve survival, most likely due to the selection of patients eligible to receive IFRT.44

In a series from the University of Toronto, Crump et al. treated 40 of 73 patients with extended-field RT to bulky sites of disease pre-ASCT. Univariate analysis determined that RT improved outcome, but this was not significant in multivariate analysis. Only disease status at transplant and relapse at irradiated sites was prognostic.45 The same group later determined that treatment-related mortality in their series was worse in patients receiving thoracic RT, particularly if significant lung volume was irradiated or if given within 50 days of ASCT.46

Pezner et al. published the City of Hope experience with cytoreductive IFRT in 29 of 86 patients, 17 of whom subsequently received conditioning regimens with total body irradiation. In-field recurrences developed in 7% of the patients. Two-year disease-free survival (DFS) was 44%. Interstitial pneumonitis occurred in only three patients. However, the utility of IFRT in this program was difficult to evaluate.47

At MSKCC, we have used accelerated fractionated IFRT as part of cytoreduction for the past 20 years with or without total lymphoid radiation. Patients receive up to 36 Gy over a 10-day period administered in twice-daily fractions. Initially, in the pregrowth factor era, mortality with the entire program was excessive, but decreased to 6% after the introduction of G-CSF and now is 1% with the use of PBPC and more aggressive transfusion practices. Although univariate analysis supports the use of IFRT, in multivariate analysis the use of IFRT is not significant because patients with widespread extranodal disease, a worse group of patients prognostically, rarely benefit from IFRT. Interestingly <15% of failures occurred at irradiated sites.1418

Recently, a small prospective study of IFRT administered pre-ASCT was reported by Dawson et al. from University of Michigan. Thirteen patients with HL received 20-36 Gy with excellent local control and a respectable 2-year FFTF of 50%, but there was a lack of association to dose or time interval pre-ASCT .48

Cytoreductive RT continues to be frequently employed in HDT/ASCT regimens, based mostly on retrospective institutional series. Significant toxicity, primarily pulmonary, has limited most protocols to IFRT, with the addition of more extensive RT to RT-naive patients.

Variability of RT doses and parameters, timing of administration, and study populations have limited the ability to compare the studies. Prospective studies will be needed to address these questions as well as concerns about late toxicity, including secondary myelodysplasia and acute leukemia.

0 0

Post a comment