Yuni K Dewaraja1, Matthew J Schipper2, Jincheng Shen3, Lauren B Smith4, Jure Murgic5, Hatice Savas6, Ehab Youssef6, Denise Regan6, Scott J Wilderman7, Peter L Roberson2, Mark S Kaminski8, Anca M Avram6. 1. Department of Radiology, University of Michigan, Ann Arbor, Michigan yuni@umich.edu. 2. Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan. 3. Department of Biostatistics, University of Michigan, Ann Arbor, Michigan. 4. Department of Pathology, University of Michigan, Ann Arbor, Michigan. 5. Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, Zagreb, Croatia. 6. Department of Radiology, University of Michigan, Ann Arbor, Michigan. 7. Department of Nuclear Engineering, University of Michigan, Ann Arbor, Michigan; and. 8. Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Abstract
UNLABELLED: 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). CONCLUSION: 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.
UNLABELLED: The study aimed at identifying patient-specific dosimetric and nondosimetric factors predicting outcome of non-Hodgkin lymphomapatients 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 lymphomapatients 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). CONCLUSION: 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.
Authors: Richard I Fisher; Mark S Kaminski; Richard L Wahl; Susan J Knox; Andrew D Zelenetz; Julie M Vose; John P Leonard; Stewart Kroll; Stanley J Goldsmith; Morton Coleman Journal: J Clin Oncol Date: 2005-09-26 Impact factor: 44.544
Authors: Bruce D Cheson; Beate Pfistner; Malik E Juweid; Randy D Gascoyne; Lena Specht; Sandra J Horning; Bertrand Coiffier; Richard I Fisher; Anton Hagenbeek; Emanuele Zucca; Steven T Rosen; Sigrid Stroobants; T Andrew Lister; Richard T Hoppe; Martin Dreyling; Kensei Tobinai; Julie M Vose; Joseph M Connors; Massimo Federico; Volker Diehl Journal: J Clin Oncol Date: 2007-01-22 Impact factor: 44.544
Authors: Thomas A Davis; Mark S Kaminski; John P Leonard; Frank J Hsu; Mary Wilkinson; Andrew Zelenetz; Richard L Wahl; Stewart Kroll; Morton Coleman; Michael Goris; Ronald Levy; Susan J Knox Journal: Clin Cancer Res Date: 2004-12-01 Impact factor: 12.531
Authors: Yuni K Dewaraja; Matthew J Schipper; Peter L Roberson; Scott J Wilderman; Hanan Amro; Denise D Regan; Kenneth F Koral; Mark S Kaminski; Anca M Avram Journal: J Nucl Med Date: 2010-06-16 Impact factor: 10.057
Authors: M S Kaminski; J Estes; K R Zasadny; I R Francis; C W Ross; M Tuck; D Regan; S Fisher; J Gutierrez; S Kroll; R Stagg; G Tidmarsh; R L Wahl Journal: Blood Date: 2000-08-15 Impact factor: 22.113
Authors: George Sgouros; Shannon Squeri; Ase M Ballangrud; Katherine S Kolbert; Jerrold B Teitcher; Katherine S Panageas; Ronald D Finn; Chaitanya R Divgi; Steven M Larson; Andrew D Zelenetz Journal: J Nucl Med Date: 2003-02 Impact factor: 10.057
Authors: R L M Haas; Ph Poortmans; D de Jong; B M P Aleman; L G H Dewit; M Verheij; A A M Hart; M H J van Oers; M van der Hulst; J W Baars; H Bartelink Journal: J Clin Oncol Date: 2003-07-01 Impact factor: 44.544
Authors: Matthew J Schipper; Kenneth F Koral; Anca M Avram; Mark S Kaminski; Yuni K Dewaraja Journal: Cancer Biother Radiopharm Date: 2012-09 Impact factor: 3.099
Authors: Peter L Roberson; Lauren B Smith; Meredith A Morgan; Matthew J Schipper; Scott J Wilderman; Anca M Avram; Mark S Kaminski; Yuni K Dewaraja Journal: Cancer Biother Radiopharm Date: 2017-10-30 Impact factor: 3.099
Authors: Abigail E Besemer; Joseph J Grudzinski; Jamey P Weichert; Lance T Hall; Bryan P Bednarz Journal: Cancer Biother Radiopharm Date: 2018-10-23 Impact factor: 3.099
Authors: Abigail E Besemer; You Ming Yang; Joseph J Grudzinski; Lance T Hall; Bryan P Bednarz Journal: Cancer Biother Radiopharm Date: 2018-04-25 Impact factor: 3.099
Authors: Emilie Roncali; Jacek Capala; Stanley H Benedict; Gamal Akabani; Bryan Bednarz; Vikram Bhadrasain; Wesley E Bolch; Jeffrey C Buchsbaum; Norman C Coleman; Yuni K Dewaraja; Eric Frey; Michael Ghaly; Joseph Grudzinski; Robert F Hobbs; Roger W Howell; John L Humm; Charles A Kunos; Steve Larson; Frank I Lin; Mark Madsen; Saed Mirzadeh; David Morse; Daniel Pryma; George Sgouros; Sara St James; Richard L Wahl; Ying Xiao; Pat Zanzonico; Katherine Zukotynski Journal: J Nucl Med Date: 2020-12-04 Impact factor: 10.057
Authors: Francesco Cicone; David Viertl; Thibaut Denoël; Michael G Stabin; John O Prior; Silvano Gnesin Journal: EJNMMI Res Date: 2022-04-11 Impact factor: 3.138
Authors: Sara St James; Bryan Bednarz; Stanley Benedict; Jeffrey C Buchsbaum; Yuni Dewaraja; Eric Frey; Robert Hobbs; Joseph Grudzinski; Emilie Roncali; George Sgouros; Jacek Capala; Ying Xiao Journal: Int J Radiat Oncol Biol Phys Date: 2020-08-14 Impact factor: 7.038