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I. J. Radiation Oncology d Biology d Physics

estimate of g50 from the randomized trials becomes 0.78 (0.46–1.09) instead of 0.84. Dr. Williams’ second, more speculative proposition, that androgen deprivation therapy (ADT) affects the steepness, not just the position, of the radiation dose–response curve, is not supported by the intermediate-high risk data (Fig. 1). The p value for heterogeneity among trials is 0.05, mainly because of the high g50-estimate from Kuban’s trial, with no obvious trend from Zietman (0% ADT) via Peeters (21% ADT) to Dearnaley (100% ADT). Low-risk patient g-estimates are more uncertain and we do not feel that any reasonable inference can be made regarding g50 and ADT. IVAN R. VOGELIUS, PH.D. Department of Oncology Rigshospitalet, University of Copenhagen Denmark SøREN M. BENTZEN, PH.D., D.SC. Department of Human Oncology University of Wisconsin School of Medicine and Public Health K4/316 Clinical Science Center 600 Highland Avenue Madison, WI doi:10.1016/j.ijrobp.2010.12.010

MARGINAL MISSES AFTER POSTOPERATIVE INTENSITY-MODULATED RADIOTHERAPY FOR HEAD AND NECK CANCER: IN REGARD TO CHEN ET AL. (INT J RADIAT ONCOL BIOL PHYS. 2010 JUL 23) To the Editor: We read with interest the report by Chen and colleagues addressing the rate of marginal misses after postoperative intensitymodulated radiotherapy (IMRT) for head-and-neck cancer (1). The primary endpoint was the incidence of geographical ‘‘marginal-field’’ misses expressed by the incidence of postoperative locoregional (LR) failure in disease control. While we acknowledge the importance of the proposed research question, we feel that the study design and subsequent conclusions were rather inaccurate. First, the authors state that positron emission tomography (PET) scans were ordered in only 20 patients (22%) before treatment. It is not clear, however, if PET scans were available and/or used retrospectively in the 6 patients under question to assess the adequacy of initial radiation dose coverage. LR recurrences picked up by follow-up PET scans might actually represent failure in original target volume coverage rather than technique related ‘‘marginal’’ miss. Technically, the authors failed to specify the average margin of organ deviation following the described ‘‘formal’’ coregistration of radiological follow-up images of tumor recurrence with the computed tomography (CT) images used in radiotherapy planning. This is of paramount importance since migration of only a few millimeters might mistakably describe an in-field failure as a ‘‘marginal’’ miss. IMRT plans are characterized by dramatic dose gradients. In this report, Chen and colleagues test the deleterious effects of steep dose falloffs rather than the adequacy of guideline clinical target volume (CTV) volumes. However, ‘‘marginal’’ misses were defined in accordance to the CTV. Relating the geographical distribution of LR recurrence to the 95% isodose line would poses as a more valid alternative and has been previously narrated by Eisbruch et al. (2) in their report regarding recurrences near the base of skull after IMRT for head-and-neck cancer. Furthermore, the authors specifically state that the contoured CTV and consequently the resultant treatment volume were inadequate in one of the clinical cases described in Figure 2. In this patient, LR treatment failure might represent plan inadequacy rather than technique-related "marginal" miss. Similarly, intraoperative tumor spillage and seedling pose as possible explanations for the two cases of dermal/subcutaneous recurrence. Chen et al. came short from laying down this perfectly reasoned scenario. All previously described study design deviancies markedly influence the reported conclusions. We believe that more meticulous assessments of the spatial distribution of LR recurrences are needed to assess the safety IMRT in head-and-neck cancers.

Volume 80, Number 2, 2011 AHMED SALEM, M.D. ABDULLA AL-RASHDAN, M.D. FAWZI ABU-HIJLE, M.D. JAMAL KHADER, M.D. SAMEH HASHEM, M.D. ABDELATIEF ALMOUSA, M.D., PH.D. Department of Radiation Oncology King Hussein Cancer Center Amman, Jordan doi:10.1016/j.ijrobp.2011.01.026 1. Chen AM, Farwell DG, Luu Q, et al. Marginal misses after postoperative intensity-modulated radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys 2010. In press. 2. Eisbruch A, Marsh LH, Dawson LA, et al. Recurrences near base of skull after IMRT for head-and-neck cancer: implications for target delineation in high neck and for parotid gland sparing. Int J Radiat Oncol Biol Phys 2004;59:28–42. IN REPLY TO SALEM ET AL. To the Editor: We thank Dr. Salem and colleagues for their thoughtful comments regarding our work and agree that retrospective limitations make drawing definitive conclusions difficult. What must be kept in mind, however, is that our study was designed not to determine the true incidence of geographic miss after postoperative intensity-modulated radiotherapy (IMRT) for head-and-neck cancer, but rather to serve as an illustrative series of cases documenting potential spatial patterns of failures. As stated in the purpose of the abstract, our objective was to ‘‘describe’’ the location of recurrences, with the goal of promoting continual assessment with respect to how target volumes are delineated. By no means was this an exact science, inasmuch as the word ‘‘marginal’’ by its very definition implies an arbitrariness and uncertainty that convey a degree of subjectivity inherent in any analysis of this nature. Indeed, definitions of ‘‘marginal’’ in the setting of IMRT vary across studies (1–3). Complicating this matter is that registration methods are far from perfect, because postirradiation scans are frequently obtained with the head and neck in a different position than at the time of simulation and treatment (4, 5). Although one can argue that the ‘‘recurrences’’ we observed may have been due to persistent disease, because positron emission tomography was not routinely performed preoperatively during the time span of the study, the fact that computed tomography failed to demonstrate any abnormalities in these regions suggests that coverage of areas at risk for disease were likely adequate. Clearly, additional studies investigating patterns of failure after IMRT for head-and-neck cancer are needed to validate our conclusions that this technology can safely be applied in the postoperative setting. ALLEN M. CHEN, M.D. JAMES A. PURDY, PH.D. University of California Davis Cancer Center Davis, CA doi:10.1016/j.ijrobp.2011.01.031 1. Eisbruch A, Marsh LH, Dawson LA, et al. Recurrences near base of skull after IMRT for head-and-neck cancer: Implications for target delineation in high neck and for parotid sparing. Int J Radiat Oncol Biol Phys 2004; 59:28–42. 2. Chao KS, Wippold FJ, Ozyigit G, et al. Determination and delineation of nodal target volumes for head-and-neck cancer based on patterns of failure in patients receiving definitive and postoperative IMRT. Int J Radiat Oncol Biol Phys 2002;53:1173–1184. 3. Sanguineti G, Gunn GB, Endres EJ, et al. Patterns of locoregional failure after exclusive IMRT for oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2008;72:737–746. 4. Hwang AB, Bacharach SL, Yom SS, et al. Can PET/computed tomography acquired in a nontreatment position be accurately registered to a head-and-neck radiotherapy planning CT? Int J Radiat Oncol Biol Phys 2009;73:578–584. 5. Ireland RH, Dyker KE, Barber DC, et al. Nonrigid image registration for head and neck cancer radiotherapy treatment planning with PET/CT. Int J Radiat Oncol Biol Phys 2007;68:952–957.

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