Tumor-Absorbed Dose Predicts Progression-Free Survival Following (131)I-Tositumomab Radioimmunotherapy.
The study aimed at identifying patient-specific dosimetric and nondosimetric factors predicting outcome of non-Hodgkin lymphoma patients after (131)I-tositumomab radioimmunotherapy for potential use in treatment planning.


METHODS
Tumor-absorbed dose measures were estimated for 130 tumors in 39 relapsed or refractory non-Hodgkin lymphoma patients by coupling SPECT/CT imaging with the Dose Planning Method (DPM) Monte Carlo code. Equivalent biologic effect was calculated to assess the biologic effects of nonuniform absorbed dose including the effects of the unlabeled antibody. Evaluated nondosimetric covariates included histology, presence of bulky disease, and prior treatment history. Tumor level outcome was based on volume shrinkage assessed on follow-up CT. Patient level outcome measures were overall response (OR), complete response (CR), and progression-free survival (PFS), determined from clinical assessments that included PET/CT.


RESULTS
The estimated mean tumor-absorbed dose had a median value of 275 cGy (range, 94-711 cGy). A high correlation was observed between tracer-predicted and therapy-delivered mean tumor-absorbed doses (P < 0.001; r = 0.85). In univariate tumor-level analysis, tumor shrinkage correlated significantly with almost all of the evaluated dosimetric factors, including equivalent biologic effect. Regression analysis showed that OR, CR, and PFS were associated with the dosimetric factors and equivalent biologic effect. Both mean tumor-absorbed dose (P = 0.025) and equivalent biologic effect (P = 0.035) were significant predictors of PFS whereas none of the nondosimetric covariates were found to be statistically significant factors affecting PFS. The most important finding of the study was that in Kaplan-Meier curves stratified by mean dose, longer PFS was observed in patients receiving mean tumor-absorbed doses greater than 200 cGy than in those receiving 200 cGy or less (median PFS, 13.6 vs. 1.9 mo for the 2 dose groups; log-rank P < 0.0001).


CONCLUSIONS
A higher mean tumor-absorbed dose was significantly predictive of improved PFS after (131)I-tositumomab radioimmunotherapy. Hence tumor-absorbed dose, which can be estimated before therapy, can potentially be used to design radioimmunotherapy protocols to improve efficacy.
Department of Radiology, University of Michigan, Ann Arbor, Michigan yuni@umich.edu.
Yuni K
YK
Dewaraja
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Matthew J
MJ
Schipper
Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
Jincheng
J
Shen
Department of Pathology, University of Michigan, Ann Arbor, Michigan.
Lauren B
LB
Smith
Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, Zagreb, Croatia.
Jure
J
Murgic
Department of Radiology, University of Michigan, Ann Arbor, Michigan.
Hatice
H
Savas
Department of Radiology, University of Michigan, Ann Arbor, Michigan.
Ehab
E
Youssef
Department of Radiology, University of Michigan, Ann Arbor, Michigan.
Denise
D
Regan
Department of Nuclear Engineering, University of Michigan, Ann Arbor, Michigan; and.
Scott J
SJ
Wilderman
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Peter L
PL
Roberson
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Mark S
MS
Kaminski
Department of Radiology, University of Michigan, Ann Arbor, Michigan.
Anca M
AM
Avram
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009010:Monte Carlo Method; D057285:Precision Medicine / Q000379:methods*; D011829:Radiation Dosage; D016499:Radioimmunotherapy; D011874:Radiometry; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden
D000911:Antibodies, Monoclonal; C119496:tositumomab I-131
SPECT/CT; dosimetry; non-Hodgkin lymphoma; progression free survival; radioimmunotherapy