Brachytherapy 13 (2014) 44e45
Editorial
Rebuttal to Drs Stone and Stock Ingrid Spadinger1, W. James Morris2,* 2
1 Department of Medical Physics, Vancouver Cancer Centre, British Columbia Cancer Agency, Vancouver, BC, Canada Department of Surgery, University of British Columbia, and Department of Radiation Oncology, Vancouver Cancer Centre, British Columbia Cancer Agency, Vancouver, BC, Canada
‘‘. a man hears what he wants to hear and disregards the rest .’’ The Boxer, 1969 lyrics by Paul Simon In this issue of Brachytherapy, rather than address any of the substantive issues raised by the facts in our article, Professors Stone and Stock attempt to reframe the debate by asking the (presumably) rhetorical question: ‘‘Does dose matter .?’’ (1) There is no question that dose matters. As Stone and Stock point out, it is known that higher doses improve biochemical and local control in external beam radiotherapy (EBRT). However, EBRT dose distributions are homogenous and reproducible, so ‘‘dose’’ can be unambiguously quantified. Allowing for some variation in target volume identification, an EBRT dose delivered at one institution can therefore be considered equivalent to the same dose delivered elsewhere. This cannot be said for low-dose-rate brachytherapy (LDR-PB), where dose distributions are inherently inhomogeneous and not easily characterized by a single metric. This inherent inhomogeneity is exacerbated by differences in treatment plan design among institutions (2), inaccurate delivery of the planned dose distribution, and the subjective nature of post-implant prostate contouring, on which all dose metrics depend. Consequently, while ‘‘Logically, a dose response for LDR-PB must exist .’’ (the second sentence of our Introduction), the dose metrics that have historically been (3, 4), and continue to be (5e8), recommended for quantifying LDR-PB do not provide unequivocal thresholds for optimal local control. The current analysis of our dataset, when combined with numerous reports from other institutions, which have identified D90 thresholds ranging from 130 (9) to 180 Gy (10), supports this assertion. Thus, as first
* Corresponding author. Department of Radiation Oncology, Vancouver Cancer Centre, British Columbia Cancer Agency, 600 W. Tenth Ave, Vancouver, BC, Canada. Tel.: þ1-604-877-6000; fax: þ1-604-877-0505. E-mail address: [email protected] (W.J. Morris).
pointed out by our group in a 2010 publication (11), which details (as does this article) a number of contributing factors in addition to dose inhomogeneity, the relevant question remains: ‘‘Is D90 a reliable quantifier of LDR-PB dose across institutions?’’ Clearly it is not. Stone and Stock assert that followup in our study is short. We remind the reader that time-specific actuarial estimates are based on the numbers at risk beyond the specified time. Our median followup is 5 years, and 349 men have a minimum followup of 8 years (median 5 9.7). This followup is comparable with, and the size of our dataset exceeds, those in references 1-6 cited. In particular, Stock and Stone’s frequently cited 1998 article reported on 134 patients with median followup of 32 months (maximum 5 72 months). The notion that short followup accounts for our results is, therefore, insupportable. With respect to the suggestion that the Phoenix definition delays failure designation, this is also not supported by the literature (12). Drs Stone and Stock assert (without rationale) that the lower dose implants are more likely to be among the patients not yet identified as biochemical failures because they are still in the process of failing. Logically, one would expect the oppositedthat insufficient dose would lead to earlier failure. In addition, because of learning curve effects, the lowest dose patients would be expected to have, on average, the longest followup. This latter point is corroborated by the data in Table 5 of our manuscript, which show that patients in the lowest D90 quintile had the longest median followup. Thus, it is unlikely that yet-to-be identified biochemical failures within the low-dose group contribute to the factors masking the dose response in our cohort. Finally, we detail four indirect lines of evidence suggesting that androgen deprivation therapy improved diseasefree survival, in part, by reducing the threshold dose required to eradicate local disease. But we consider the mechanism proposed by Stone and Stock (short-term androgen deprivation therapy results in a long-term delay in biochemical failure) to be implausible, given the short duration of ADT relative to median followup.
1538-4721/$ - see front matter Ó 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.brachy.2013.11.010
I. Spadinger, W.J. Morris / Brachytherapy 13 (2014) 44e45
References [1] Stone NN, Stock R. Does dose matter? Editorial Comments to Morris, et al Whole prostate D90 and V100: A doseeresponse analysis of 2000 consecutive 125I monotherapy cases. Brachytherapy 2014;13:42e43. [2] Merrick GS, Butler WM, Wallner KE, et al. Variability of prostate brachytherapy pre-implant dosimetry: A multi-institutional analysis. Brachytherapy 2005;4:241e251. [3] Nag S, Beyer D, Friedland J, et al. American Brachytherapy Society (ABS) recommendations for transperineal permanent brachytherapy of prostate cancer. Int J Radiat Oncol Biol Phys 1999;44:789e799. [4] Ash D, Flynn A, Battermann J, et al. ESTRO/EAU/EORTC recommendations on permanent seed implantation for localized prostate cancer. Radiother Oncol 2000;57:315e321. [5] Salembiera C, Lavagninib P, Nicker P, et al. Tumour and target volumes in permanent prostate brachytherapy: A supplement to the ESTRO/EAU/EORTC recommendations on prostate brachytherapy. Radiother Oncol 2007;83:3e10. [6] Nath R, Bice WS, Butler WM, et al. AAPM recommendations on dose prescription and reporting methods for permanent interstitial brachytherapy for prostate cancer: Report of Task Group No. 137. Med Phys 2009;36:5310e5322.
45
[7] Rosenthal SA, Bittner NHJ, Beyer DC, et al. American Society for Radiation Oncology (ASTRO) and American College of Radiology (ACR) practice guideline for the transperineal permanent brachytherapy of prostate cancer. Int J Radiat Oncol Biol Phys 2011;79: 335e341. [8] Davis BJ, Horwitz EM, Lee WR, et al. American Brachytherapy Society consensus guidelines for transrectal ultrasound-guided permanent prostate brachytherapy. Brachytherapy 2012;11:6e19. [9] Zelefsky MJ, Kuban DH, Levy LB, et al. Multi-institutional analysis of long-term outcomes for stages T1-T2 prostate cancer treated with permanent seed implantation. Int J Radiat Oncol Biol Phys 2007;67: 327e333. [10] Kao J, Stone NN, Lavaf A, et al. 125 I monotherapy using D90 implant doses of 180 Gy or greater. Int J Radiat Oncol Biol Phys 2008;70:96e101. [11] Morris WJ, Halperin R, Spadinger I. Point: The relationship between postimplant dose metrics and biochemical no evidence of disease following low dose rate prostate brachytherapy: Is there an elephant in the room? Brachytherapy 2010;9:289e292. [12] Kuban DA, Levy LB, Potters L, et al. Comparison of biochemical failure definitions for permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 2006;65:1487e1493.
Editorial
Rebuttal to Drs Stone and Stock Ingrid Spadinger1, W. James Morris2,* 2
1 Department of Medical Physics, Vancouver Cancer Centre, British Columbia Cancer Agency, Vancouver, BC, Canada Department of Surgery, University of British Columbia, and Department of Radiation Oncology, Vancouver Cancer Centre, British Columbia Cancer Agency, Vancouver, BC, Canada
‘‘. a man hears what he wants to hear and disregards the rest .’’ The Boxer, 1969 lyrics by Paul Simon In this issue of Brachytherapy, rather than address any of the substantive issues raised by the facts in our article, Professors Stone and Stock attempt to reframe the debate by asking the (presumably) rhetorical question: ‘‘Does dose matter .?’’ (1) There is no question that dose matters. As Stone and Stock point out, it is known that higher doses improve biochemical and local control in external beam radiotherapy (EBRT). However, EBRT dose distributions are homogenous and reproducible, so ‘‘dose’’ can be unambiguously quantified. Allowing for some variation in target volume identification, an EBRT dose delivered at one institution can therefore be considered equivalent to the same dose delivered elsewhere. This cannot be said for low-dose-rate brachytherapy (LDR-PB), where dose distributions are inherently inhomogeneous and not easily characterized by a single metric. This inherent inhomogeneity is exacerbated by differences in treatment plan design among institutions (2), inaccurate delivery of the planned dose distribution, and the subjective nature of post-implant prostate contouring, on which all dose metrics depend. Consequently, while ‘‘Logically, a dose response for LDR-PB must exist .’’ (the second sentence of our Introduction), the dose metrics that have historically been (3, 4), and continue to be (5e8), recommended for quantifying LDR-PB do not provide unequivocal thresholds for optimal local control. The current analysis of our dataset, when combined with numerous reports from other institutions, which have identified D90 thresholds ranging from 130 (9) to 180 Gy (10), supports this assertion. Thus, as first
* Corresponding author. Department of Radiation Oncology, Vancouver Cancer Centre, British Columbia Cancer Agency, 600 W. Tenth Ave, Vancouver, BC, Canada. Tel.: þ1-604-877-6000; fax: þ1-604-877-0505. E-mail address: [email protected] (W.J. Morris).
pointed out by our group in a 2010 publication (11), which details (as does this article) a number of contributing factors in addition to dose inhomogeneity, the relevant question remains: ‘‘Is D90 a reliable quantifier of LDR-PB dose across institutions?’’ Clearly it is not. Stone and Stock assert that followup in our study is short. We remind the reader that time-specific actuarial estimates are based on the numbers at risk beyond the specified time. Our median followup is 5 years, and 349 men have a minimum followup of 8 years (median 5 9.7). This followup is comparable with, and the size of our dataset exceeds, those in references 1-6 cited. In particular, Stock and Stone’s frequently cited 1998 article reported on 134 patients with median followup of 32 months (maximum 5 72 months). The notion that short followup accounts for our results is, therefore, insupportable. With respect to the suggestion that the Phoenix definition delays failure designation, this is also not supported by the literature (12). Drs Stone and Stock assert (without rationale) that the lower dose implants are more likely to be among the patients not yet identified as biochemical failures because they are still in the process of failing. Logically, one would expect the oppositedthat insufficient dose would lead to earlier failure. In addition, because of learning curve effects, the lowest dose patients would be expected to have, on average, the longest followup. This latter point is corroborated by the data in Table 5 of our manuscript, which show that patients in the lowest D90 quintile had the longest median followup. Thus, it is unlikely that yet-to-be identified biochemical failures within the low-dose group contribute to the factors masking the dose response in our cohort. Finally, we detail four indirect lines of evidence suggesting that androgen deprivation therapy improved diseasefree survival, in part, by reducing the threshold dose required to eradicate local disease. But we consider the mechanism proposed by Stone and Stock (short-term androgen deprivation therapy results in a long-term delay in biochemical failure) to be implausible, given the short duration of ADT relative to median followup.
1538-4721/$ - see front matter Ó 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.brachy.2013.11.010
I. Spadinger, W.J. Morris / Brachytherapy 13 (2014) 44e45
References [1] Stone NN, Stock R. Does dose matter? Editorial Comments to Morris, et al Whole prostate D90 and V100: A doseeresponse analysis of 2000 consecutive 125I monotherapy cases. Brachytherapy 2014;13:42e43. [2] Merrick GS, Butler WM, Wallner KE, et al. Variability of prostate brachytherapy pre-implant dosimetry: A multi-institutional analysis. Brachytherapy 2005;4:241e251. [3] Nag S, Beyer D, Friedland J, et al. American Brachytherapy Society (ABS) recommendations for transperineal permanent brachytherapy of prostate cancer. Int J Radiat Oncol Biol Phys 1999;44:789e799. [4] Ash D, Flynn A, Battermann J, et al. ESTRO/EAU/EORTC recommendations on permanent seed implantation for localized prostate cancer. Radiother Oncol 2000;57:315e321. [5] Salembiera C, Lavagninib P, Nicker P, et al. Tumour and target volumes in permanent prostate brachytherapy: A supplement to the ESTRO/EAU/EORTC recommendations on prostate brachytherapy. Radiother Oncol 2007;83:3e10. [6] Nath R, Bice WS, Butler WM, et al. AAPM recommendations on dose prescription and reporting methods for permanent interstitial brachytherapy for prostate cancer: Report of Task Group No. 137. Med Phys 2009;36:5310e5322.
45
[7] Rosenthal SA, Bittner NHJ, Beyer DC, et al. American Society for Radiation Oncology (ASTRO) and American College of Radiology (ACR) practice guideline for the transperineal permanent brachytherapy of prostate cancer. Int J Radiat Oncol Biol Phys 2011;79: 335e341. [8] Davis BJ, Horwitz EM, Lee WR, et al. American Brachytherapy Society consensus guidelines for transrectal ultrasound-guided permanent prostate brachytherapy. Brachytherapy 2012;11:6e19. [9] Zelefsky MJ, Kuban DH, Levy LB, et al. Multi-institutional analysis of long-term outcomes for stages T1-T2 prostate cancer treated with permanent seed implantation. Int J Radiat Oncol Biol Phys 2007;67: 327e333. [10] Kao J, Stone NN, Lavaf A, et al. 125 I monotherapy using D90 implant doses of 180 Gy or greater. Int J Radiat Oncol Biol Phys 2008;70:96e101. [11] Morris WJ, Halperin R, Spadinger I. Point: The relationship between postimplant dose metrics and biochemical no evidence of disease following low dose rate prostate brachytherapy: Is there an elephant in the room? Brachytherapy 2010;9:289e292. [12] Kuban DA, Levy LB, Potters L, et al. Comparison of biochemical failure definitions for permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 2006;65:1487e1493.
