298
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Letters to the Editor
From: Alexander S. Pasciak, PhD Austin C. Bourgeois, MD The Johns Hopkins University School of Medicine (A.S.P.) Baltimore, Maryland Department of Radiology (A.S.P., A.C.B.) University of Tennessee Graduate School of Medicine University of Tennessee Medical Center 1924 Alcoa Highway Knoxville, TN 37920 Department of Radiology (A.C.B.) Medical University of South Carolina Charleston, South Carolina
Editor: A recent article in JVIR described a retrospective evaluation of the body surface area (BSA) treatment planning method for yttrium-90 radioembolization using resin microspheres in a cohort of 283 treated patients (1). In this work, Grosser et al (1) used these data to point out potential shortcomings with the BSA model and suggest that its use could lead to “overdosage and underdosage … in individual patients.” Although we agree that the BSA method is far from perfect, as correctly pointed out by Grosser et al (1), we also believe there are several important points that the JVIR readership should be aware of when interpreting this paper. Grosser et al (1) present much of their results in terms of activity concentration (AC) averaged over the whole liver volume. Although the use of AC is similar to the average whole liver dose used in a previous article on the BSA method by Lam et al (2), there is one critical difference: The analysis by Lam et al included only patients treated with single-session, whole-liver radioembolization. The patient cohort described in Grosser et al (1) was not limited to whole-liver treatment, yet the authors explicitly state that “prescribed activities” were normalized by the total liver volume to obtain the AC figure of merit. In patients not treated in a single-session bilobar fashion, this normalization has the effect of artificially decreasing AC because the total liver volume normalization factor includes tissue that was not treated. The average absorbed dose to treated liver tissue would have been a more useful figure of merit, which might have resulted in a more favorable relationship (eg, in Figure 2b in the article) (1). Although the method by which AC was used was a point of potential confusion in the analysis by Grosser et al (1), we believe that their general results (ie, see Table 4 in the article) are correct and logical given the construction of the BSA model. The BSA model does not account for liver volume, which may be viewed as a “methodologic shortcoming” of the model, as suggested by the authors. However, the authors’ contention that the BSA model could result in “overdosage and underdosage … in individual patients” is not supported by their data except by pointing out differences in AC for individual
Grosser et al
’
JVIR
patients with outlying liver volumes within their cohort. To determine if underdosage or overdosage occurred in this study cohort (1), an analysis of tumor response, liver toxicity, and adverse events and, ideally, quantification of absorbed dose in the liver from imaging obtained after radioembolization would be required. Because no such data from the outcomes of these patients were included, these points from the authors’ discussion and conclusion should be interpreted with caution. That said, we agree that yttrium-90 radioembolization using resin microspheres has the potential to be more beneficial with a more patientspecific treatment planning method.
REFERENCES 1. Grosser OS, Ulrich G, Furth C, et al. Intrahepatic activity distribution in radioembolization with yttrium-90-labeled resin microspheres using the body surface area method—a less than perfect model. J Vasc Interv Radiol 2015; 26:1615–1621. 2. Lam MG, Louie JD, Abdelmaksoud MH, et al. Limitations of body surface area-based activity calculation for radioembolization of hepatic metastases in colorectal cancer. J Vasc Interv Radiol 2014; 25:1085–1093.
Drs. Grosser et al respond : We appreciate the opportunity to respond to the letter to the editor. We agree with the authors that the body surface area (BSA) method is far from a perfect model for activity calculation in radioembolization. Nevertheless, it is frequently used in clinical practice and has been approved by regulatory bodies for activity calculation in yttrium-90 radioembolization (RE) with resin-based microspheres. In order to improve RE, model-based limitations and constraints must be understood. The aim of our study (1) was therefore to assess the model-based effects in preradioembolization activity calculation. According to our data, we were able to show that the poor correlation of BSA and actual liver volume, combined with the negligibility of absolute liver and tumor volumes, may result in a high variability of the prescribed activity (see Equation 3 in the article [1]). To address a concern regarding the normalization of the prescribed activity expressed in the letter, we refer to the section of our paper entitled Determination of Activity Concentrations (ACs) (1). The normalized AC (see Equation 5 in the article [1]) was calculated from the activity prescribed by the BSA method for a whole-liver treatment (see Equation 3 in the article [1]), as all data necessary for dose calculation had been derived from the whole-liver evaluation. In the case of lobar/segmental RE in further clinical workup, the prescribed activity is reduced in proportion to the treated liver volume. O.S.G. and J.Ri. are paid consultants for Sirtex (North Sydney, Australia) outside the submitted work. H.A. received funding from Sirtex during the conduct of the study. J.Ri. has received funding from Sirtex outside the submitted work. The other author has not identified a conflict of interest. http://dx.doi.org/10.1016/j.jvir.2015.11.036
Volume 27
’
Number 2
’
February
’
2016
In our analysis of the BSA method, AC was consistently calculated for a whole liver. Therefore, concerns that the lobar treatment activities used for actual therapy were correlated to the whole liver volume are unsubstantiated. Moreover, we want to emphasize that significant differences in AC were observed in all liver volume groups (see Fig 2b and Table 5 in the article [1]) and not only in “individual patients with outlying liver volumes.” We totally agree that assumptions about the efficacy of RE can only be made in a clinical setting, taking, eg, the response to therapy, liver toxicity, absorbed tumor doses, and stasis into account. This was decidedly addressed in the second-to-last paragraph of the Discussion section of our paper (1). Nevertheless, one cannot ignore the fact that these factors are linked to the initial model-based prescribed activity. Therefore, the assumption—carefully formulated, in our opinion—that “overdosage and underdosage of RE may occur in individual patients” is justified. In summary, the poor correlation of BSA and liver volume in our study (1), as well as the negligibility of the liver volume (also observed by Lam et al [2]), should be respected in the planning of prospective clinical trials
299
with the BSA method to prevent a systematic bias in activity calculation. Oliver S. Grosser, PhD Holger Amthauer, MD Jens Ricke, MD Juri Ruf, MD Department of Radiology and Nuclear Medicine (O.S.G., H.A., J.Ri.) University Hospital Magdeburg Leipziger Strasse 44 Magdeburg 39120, Germany; and Department of Nuclear Medicine (J.Ru.) University Hospital Freiburg Freiburg, Germany
REFERENCES 1. Grosser OS, Ulrich G, Furth C, et al. Intrahepatic activity distribution in radioembolization with yttrium-90-labeled resin microspheres using the body surface area method—a less than perfect model. J Vasc Interv Radiol 2015; 26:1615–1621. 2. Lam MG, Louie JD, Abdelmaksoud MH, et al. Limitations of body surface area-based activity calculation for radioembolization of hepatic metastases in colorectal cancer. J Vasc Interv Radiol 2014; 25:1085–1093.
’
Letters to the Editor
From: Alexander S. Pasciak, PhD Austin C. Bourgeois, MD The Johns Hopkins University School of Medicine (A.S.P.) Baltimore, Maryland Department of Radiology (A.S.P., A.C.B.) University of Tennessee Graduate School of Medicine University of Tennessee Medical Center 1924 Alcoa Highway Knoxville, TN 37920 Department of Radiology (A.C.B.) Medical University of South Carolina Charleston, South Carolina
Editor: A recent article in JVIR described a retrospective evaluation of the body surface area (BSA) treatment planning method for yttrium-90 radioembolization using resin microspheres in a cohort of 283 treated patients (1). In this work, Grosser et al (1) used these data to point out potential shortcomings with the BSA model and suggest that its use could lead to “overdosage and underdosage … in individual patients.” Although we agree that the BSA method is far from perfect, as correctly pointed out by Grosser et al (1), we also believe there are several important points that the JVIR readership should be aware of when interpreting this paper. Grosser et al (1) present much of their results in terms of activity concentration (AC) averaged over the whole liver volume. Although the use of AC is similar to the average whole liver dose used in a previous article on the BSA method by Lam et al (2), there is one critical difference: The analysis by Lam et al included only patients treated with single-session, whole-liver radioembolization. The patient cohort described in Grosser et al (1) was not limited to whole-liver treatment, yet the authors explicitly state that “prescribed activities” were normalized by the total liver volume to obtain the AC figure of merit. In patients not treated in a single-session bilobar fashion, this normalization has the effect of artificially decreasing AC because the total liver volume normalization factor includes tissue that was not treated. The average absorbed dose to treated liver tissue would have been a more useful figure of merit, which might have resulted in a more favorable relationship (eg, in Figure 2b in the article) (1). Although the method by which AC was used was a point of potential confusion in the analysis by Grosser et al (1), we believe that their general results (ie, see Table 4 in the article) are correct and logical given the construction of the BSA model. The BSA model does not account for liver volume, which may be viewed as a “methodologic shortcoming” of the model, as suggested by the authors. However, the authors’ contention that the BSA model could result in “overdosage and underdosage … in individual patients” is not supported by their data except by pointing out differences in AC for individual
Grosser et al
’
JVIR
patients with outlying liver volumes within their cohort. To determine if underdosage or overdosage occurred in this study cohort (1), an analysis of tumor response, liver toxicity, and adverse events and, ideally, quantification of absorbed dose in the liver from imaging obtained after radioembolization would be required. Because no such data from the outcomes of these patients were included, these points from the authors’ discussion and conclusion should be interpreted with caution. That said, we agree that yttrium-90 radioembolization using resin microspheres has the potential to be more beneficial with a more patientspecific treatment planning method.
REFERENCES 1. Grosser OS, Ulrich G, Furth C, et al. Intrahepatic activity distribution in radioembolization with yttrium-90-labeled resin microspheres using the body surface area method—a less than perfect model. J Vasc Interv Radiol 2015; 26:1615–1621. 2. Lam MG, Louie JD, Abdelmaksoud MH, et al. Limitations of body surface area-based activity calculation for radioembolization of hepatic metastases in colorectal cancer. J Vasc Interv Radiol 2014; 25:1085–1093.
Drs. Grosser et al respond : We appreciate the opportunity to respond to the letter to the editor. We agree with the authors that the body surface area (BSA) method is far from a perfect model for activity calculation in radioembolization. Nevertheless, it is frequently used in clinical practice and has been approved by regulatory bodies for activity calculation in yttrium-90 radioembolization (RE) with resin-based microspheres. In order to improve RE, model-based limitations and constraints must be understood. The aim of our study (1) was therefore to assess the model-based effects in preradioembolization activity calculation. According to our data, we were able to show that the poor correlation of BSA and actual liver volume, combined with the negligibility of absolute liver and tumor volumes, may result in a high variability of the prescribed activity (see Equation 3 in the article [1]). To address a concern regarding the normalization of the prescribed activity expressed in the letter, we refer to the section of our paper entitled Determination of Activity Concentrations (ACs) (1). The normalized AC (see Equation 5 in the article [1]) was calculated from the activity prescribed by the BSA method for a whole-liver treatment (see Equation 3 in the article [1]), as all data necessary for dose calculation had been derived from the whole-liver evaluation. In the case of lobar/segmental RE in further clinical workup, the prescribed activity is reduced in proportion to the treated liver volume. O.S.G. and J.Ri. are paid consultants for Sirtex (North Sydney, Australia) outside the submitted work. H.A. received funding from Sirtex during the conduct of the study. J.Ri. has received funding from Sirtex outside the submitted work. The other author has not identified a conflict of interest. http://dx.doi.org/10.1016/j.jvir.2015.11.036
Volume 27
’
Number 2
’
February
’
2016
In our analysis of the BSA method, AC was consistently calculated for a whole liver. Therefore, concerns that the lobar treatment activities used for actual therapy were correlated to the whole liver volume are unsubstantiated. Moreover, we want to emphasize that significant differences in AC were observed in all liver volume groups (see Fig 2b and Table 5 in the article [1]) and not only in “individual patients with outlying liver volumes.” We totally agree that assumptions about the efficacy of RE can only be made in a clinical setting, taking, eg, the response to therapy, liver toxicity, absorbed tumor doses, and stasis into account. This was decidedly addressed in the second-to-last paragraph of the Discussion section of our paper (1). Nevertheless, one cannot ignore the fact that these factors are linked to the initial model-based prescribed activity. Therefore, the assumption—carefully formulated, in our opinion—that “overdosage and underdosage of RE may occur in individual patients” is justified. In summary, the poor correlation of BSA and liver volume in our study (1), as well as the negligibility of the liver volume (also observed by Lam et al [2]), should be respected in the planning of prospective clinical trials
299
with the BSA method to prevent a systematic bias in activity calculation. Oliver S. Grosser, PhD Holger Amthauer, MD Jens Ricke, MD Juri Ruf, MD Department of Radiology and Nuclear Medicine (O.S.G., H.A., J.Ri.) University Hospital Magdeburg Leipziger Strasse 44 Magdeburg 39120, Germany; and Department of Nuclear Medicine (J.Ru.) University Hospital Freiburg Freiburg, Germany
REFERENCES 1. Grosser OS, Ulrich G, Furth C, et al. Intrahepatic activity distribution in radioembolization with yttrium-90-labeled resin microspheres using the body surface area method—a less than perfect model. J Vasc Interv Radiol 2015; 26:1615–1621. 2. Lam MG, Louie JD, Abdelmaksoud MH, et al. Limitations of body surface area-based activity calculation for radioembolization of hepatic metastases in colorectal cancer. J Vasc Interv Radiol 2014; 25:1085–1093.
