Impact of nodal regression on radiation dose for lymphoma patients after radioimmunotherapy.
Radioimmunotherapy for non-Hodgkin's lymphoma often results in surprisingly high response rates compared with those expected from estimated absorbed radiation doses. Several factors, including radiobiologic response, selective targeting, and heterogeneous absorbed radiation within the lymphoma, are likely to contribute to the lack of a dose-response relationship. This article investigates the impact of nodal regression on absorbed radiation dose and applies a correction factor to account for its effect.


METHODS
The radioactivity in and regression of 37 superficial lymph nodes were measured in 7 non-Hodgkin's lymphoma patients treated with 775-3,450 MBq/m(2) of (131)I-Lym-1 monoclonal antibody. Nodal dimensions were measured with calipers and radioactivity was quantitated using gamma-camera imaging on multiple days after (131)I-Lym-1 injection. Both nodal regression and radioactivity were fit with monoexponential functions. Formulas were developed to account for simultaneous change in nodal mass and radioactivity. All lymph nodes with size and radioactivity measurements, and exponential-fit coefficients of determination of >0.8, were included in the analysis.


RESULTS
A 3 orders-of-magnitude node-to-node variation in initial radiopharmaceutical concentration (MBq/g) was observed, with the highest concentrations in the smallest nodes. Reduction in radioactivity as a function of time (biologic half-life) varied by about a factor of 2. In contrast, the rate of nodal regression varied by orders of magnitude, from a 14-h half-time to no regression at all. Five nodes regressed with a half-time that was shorter than their observed effective radiopharmaceutical half-life. Accounting for the effect of nodal regression resulted in dose corrections ranging from 1 (no correction) to a factor of >10, with 70% of nodes requiring a correction factor of at least 20% and >50% of nodes requiring a correction factor of >2. Corrected for nodal regression, 46% of nodes analyzed had absorbed radiation doses of >10 Gy and 32% had doses of >20 Gy.


CONCLUSIONS
These results highlight the importance of accounting for change in mass, particularly tumor regression, when assessing absorbed radiation dose for tissues whose mass changes during the time the radiation dose is being absorbed. The increase in calculated absorbed dose when this change is considered provides better insight into the high nodal response rates observed in non-Hodgkin's lymphoma patients.
Hartmann Siantar
Christine L
CL
Glenn T. Seaborg Institute, Lawrence Livermore National Laboratory, PO Box 808, Livermore, CA 94550, USA. chs@llnl.gov
DeNardo
Gerald L
GL
DeNardo
Sally J
SJ
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D003198:Computer Simulation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008198:Lymph Nodes / Q000473:pathology* / Q000528:radiation effects*; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology* / Q000532:radiotherapy*; D008297:Male; D008954:Models, Biological; D016499:Radioimmunotherapy / Q000379:methods*; D011874:Radiometry / Q000379:methods; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D012074:Remission Induction; D013223:Statistics as Topic; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007457:Iodine Radioisotopes; C410509:Lym-1 monoclonal antibody; D019275:Radiopharmaceuticals