Regarding Relative Toxicities of Stereotactic Body ...

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Sep 2, 2014 - (IMRT) for prostate cancer, Yu et al compare two contemporary. “state of the art” ... is dose,” and a PSA nadir of zero does not come for free. Some patients will ... ment with SBRT. And of course, if the end result is arguably a.

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32



NUMBER

30



OCTOBER

20

2014

JOURNAL OF CLINICAL ONCOLOGY

Regarding Relative Toxicities of Stereotactic Body Radiation Therapy Versus Intensity-Modulated Radiation Therapy for Prostate Cancer TO THE EDITOR: In their report of stereotactic body radiation therapy (SBRT) versus intensity-modulated radiation therapy (IMRT) for prostate cancer, Yu et al compare two contemporary “state of the art” modalities.1 This important and seemingly simple comparison is problematic on a number of fronts. Regarding efficacy and toxicity of SBRT versus IMRT, we have a unique opportunity to observe both modalities simultaneously. Our practice treats a large volume of IMRT and SBRT patients, including treatment under three separate institutional review board–approved prostate SBRT protocols.2-4 We have also used brachytherapy to treat many patients with prostate cancer. Clinically, the urinary tract adverse effect profile for SBRT may be greater than that seen with conventional IMRT for some patients; however, the adverse effects are typically still self-limited, medically manageable, and definitely not greater than those seen with prostate brachytherapy. Thus, the toxicity range of prostate SBRT falls squarely within the range of clinically acceptable GU toxicity, relative to the larger universe of all currently practiced radiotherapy methods. Our observed GI toxicity with prostate SBRT is virtually nonexistent, with grade 2 and grade 3 GI toxicity incidence being 2% and 0%, respectively.5 From a radiobiologic viewpoint, SBRT delivers a larger biologic dose equivalent to the prostate compared with conventional fractionation, assuming the alpha:beta ratio for this disease to be ⱕ 3 Gy.6 In fact, the SBRT dose equivalent may be significantly higher, depending on the specific technique and fractionation. Reported PSA nadir levels of 0.1 ng/mL post-SBRT support this assertion.5,7,8 The higher equivalent dose for SBRT versus IMRT predicts a lower PSA nadir and a lower rate of biochemical relapse at the cost of potentially higher GU toxicity. The exact same trade-off was described by Zelefsky et al, in the comparison of 125I prostate brachytherapy versus IMRT.9 Their brachytherapy patients had a lower PSA nadir, a lower biochemical relapse rate, and a higher grade 2 GU and GI toxicity incidence relative to their simultaneous IMRT cohort. Whether the prostate dose escalation mechanism is provided by brachytherapy or SBRT, we need to manage toxicity and disease-response expectations appropriately for our patients, allowing each individual to make the best therapeutic decision to match his own specific priorities. Stated even more simply: “Dose is dose,” and a PSA nadir of zero does not come for free. Some patients will willingly trade a somewhat higher degree of potential urinary tract toxicity in exchange for a potentially higher cure rate, whereas others will not. Journal of Clinical Oncology, Vol 32, No 30 (October 20), 2014: pp 3455

C O R R E S P O N D E N C E

Finally, not all prostate SBRT or IMRT regimens are created equal. A wide range of SBRT regimens, from 33.5 Gy in five fractions to 38 Gy in four fractions, have been described, each with its own toxicity and curative potential profile. IMRT regimens of 74 Gy in 34 fractions, 81 Gy in 45 fractions, 80 Gy in 40 fractions, 86.4 Gy in 48 fractions, and 70 Gy in 28 fractions have been described. A surrogate database analysis such as the one performed by Yu et al obviously has zero capability to evaluate which specific SBRT or IMRT regimens are more or less problematic. An analysis of either SBRT or IMRT alone could yield similar differential toxicity outcomes if lower and higher dose regimens were compared, and in fact, this result has been reported.8,10 Of course this would be yet another reaffirmation of the statement “Dose is dose.” In summary, there is a high degree of user programmability and patient variability involved with either SBRT or IMRT. As such, it is far too simplistic to declare either modality as superior or inferior to the other in any way, particularly from a study method such as the SEER data-based analysis reported by Yu et al, which has no ability to account for technical variations, patient-specific risk factors, or specific complication severity. Both of these contemporary modalities will be successful if skillfully applied, and either could be toxic and/or ineffective if less rigorously practiced. Finally, this analysis indicated a lower average total cost of treatment with SBRT. And of course, if the end result is arguably a “push,” then the method with the lower cost becomes more attractive indeed.

Donald B. Fuller Genesis Healthcare Partners, CyberKnife Centers of San Diego, San Diego, CA

AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Disclosures provided by the authors are available with this article at www.jco.org. REFERENCES 1. Yu JB, Cramer LD, Herrin J, et al: Stereotactic body radiation therapy versus intensity-modulated radiation therapy for prostate cancer: Comparison of toxicity. J Clin Oncol 32:1195-1201, 2014 2. Fuller DB: CyberKnife Radiosurgery for Locally Recurrent Prostate CA. Bethesda, MD, National Library of Medicine, 2009 3. Fuller DB: CyberKnife Radiosurgery for Localized Prostatic Carcinoma. Bethesda, MD, National Library of Medicine, 2010 4. Fuller DB, Mardirossian G: CyberKnife Radiosurgery For Low & Intermediate Risk Prostate Cancer: Emulating HDR Brachytherapy Dosimetry. Bethesda, MD, National Library of Medicine, 2008 5. Fuller DB, Mardirossian G, Wong D, et al: Prospective evaluation of stereotactic body radiation therapy for low- and intermediate-risk prostate cancer: Emulating high-dose-rate brachytherapy dose distribution Int J Radiat Oncol Biol Phys 84:S149, 2012 6. Fowler JF, Toma-Dasu I, Dasu A: Is the a´/aˆratio for prostate tumours really low and does it vary with the level of risk at diagnosis? Anticancer Res 33:1009-1011, 2013 7. Katz AJ, Santoro M, Diblasio F, et al: Stereotactic body radiotherapy for localized prostate cancer: Disease control and quality of life at 6 years. Radiat Oncol 8:118, 2013

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8. Katz AJ, Kang J: Stereotactic body radiation therapy for low-, intermediate-, and high-risk prostate cancer: Disease control and quality of life at 6 years. Int J Radiat Oncol Biol Phys 87:S24-S25, 2013 9. Zelefsky MJ, Yamada Y, Pei X, et al: Comparison of tumor control and toxicity outcomes of high-dose intensity-modulated radiotherapy and brachytherapy for patients with favorable risk prostate cancer. Urology 77:986-990, 2011

10. Syndikus I, Morgan RC, Sydes MR, et al: Late gastrointestinal toxicity after dose-escalated conformal radiotherapy for early prostate cancer: Results from the UK Medical Research Council RT01 trial (ISRCTN47772397). Int J Radiat Oncol Biol Phys 77:773-783, 2010

DOI: 10.1200/JCO.2014.56.5572; published online ahead of print at www.jco.org on September 2, 2014

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© 2014 by American Society of Clinical Oncology

JOURNAL OF CLINICAL ONCOLOGY

Downloaded from jco.ascopubs.org on September 22, 2015. For personal use only. No other uses without permission. Copyright © 2014 American Society of Clinical Oncology. All rights reserved.

Correspondence

AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Regarding Relative Toxicities of Stereotactic Body Radiation Therapy Versus Intensity-Modulated Radiation Therapy for Prostate Cancer The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I ⫽ Immediate Family Member, Inst ⫽ My Institution. For a detailed description of the disclosure categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Donald B. Fuller Stock or Other Ownership: Varian Medical Systems Accuray

www.jco.org

Consulting or Advisory Role: Accuray Research Funding: Accuray (Inst)

© 2014 by American Society of Clinical Oncology

Downloaded from jco.ascopubs.org on September 22, 2015. For personal use only. No other uses without permission. Copyright © 2014 American Society of Clinical Oncology. All rights reserved.

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