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What Is the Target Volume for Preoperative Accelerated Partial Breast Irradiation (APBI)? In Regards to Nichols et al. (Int J Radiat Oncol Biol Phys 2010;77:197–202) and Palta et al. (Int J Radiat Oncol Biol Phys 2010, in Press)
Int. J. Radiation Oncology Biol. Phys., Vol. 80, No. 1, pp. 314–317, 2011 Copyright Ó 2011 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/$ - see front matter
LETTERS TO THE EDITOR 2. Harris JR, Levene MB, Svensson G, et al. Analysis of cosmetic results following primary radiation therapy for stages I and II carcinoma of the breast. Int J Radiat Oncol Biol Phys 1979;5:257–261. 3. Pezner RD, Patterson MP, Hill LR, Vora N, Desai KR, Archambeau JO, et al. Breast retraction assessment: An objective evaluation of cosmetic results of patients treated conservatively for breast cancer. Int J Radiat Oncol Biol Phys 1985;11:575–578. 4. Tsouskas LI, Fentiman IS. Breast compliance: a new method for evaluation of cosmetic outcome after conservative treatment of early breast cancer. Breast Cancer Res Treat 1990;15:185–190. 5. van Limbergen E, van der Schueren E, van Tongelen K. Cosmetic evaluation of breast conserving treatment for mammary cancer. 1. Proposal of a quantitative scoring system. Radiother Oncol 1989;16:159–167. 6. Triedman SA, Osteen R, Harris JR. Factors influencing cosmetic outcome of conservative surgery and radiotherapy for breast cancer. Surg Clin North Am 1990;70:901–916. 7. Cardoso MJ, Cardoso J, Amaral N, et al. Turning subjective into objective: The BCCT core software for evaluation of cosmetic results in breast cancer conservative treatment. The Breast 2007;16: 456–461. 8. Leonardi MC, Garusi C, Santoro L, et al. Impact of the medical discipline and observer gender on cosmetic outcome evaluation in breast reconstruction using transverse rectus abdominis myocutaneous (TRAM) flap and radiotherapy. J Plast Reconstr Aesthet Surg 2000 Dec;63(12): 2091–2097. 9. Wernicke AG, Parashar B, Kulidzhanov F, et al. Prospective study validating inter- and intraobserver variability of tissue compliance meter in breast tissue of healthy volunteers: Potential implications for patients with radiation-induced fibrosis of the breast. Int J Radiat Oncol Biol Phys. 2010;80:39–46. 10. Collette S, Collette L, Budiharto T. Predictors of the risk of fibrosis at 10 years after breast conserving therapy for early breast cancer: A study based on the EORTC Trial 22881–10882 ‘boost versus no boost’. Eur J Cancer 2008;44:2587–2599. Erratum in Eur J Cancer 2009;45:2061.
IMPACT OF THE RADIATION BOOST ON OUTCOMES AFTER BREAST-CONSERVING SURGERY AND RADIATION: IN REGARD TO MURPHY C, ET AL. (INT J RADIAT ONCOL BIOL PHYS IN PRESS) To the Editor: We have read with profound interest the article by Murphy et al., ‘‘Impact of the radiation boost on outcomes after breast-conserving surgery and radiation’’ (1). The authors are commended for pointing out that a boost is not always necessary in all patients. We have found, however, a few points that deserve consideration. a) The cosmetic result after radiotherapy was scored by the 4-point scale (2). The most usual method using the Harvard scale is subjective as it evaluates a patient’s appearance on a photograph and has frequently used personnel involved in the treatment process for this purpose. The objective methods use measurements taken from the patient or from photographs, and are based essentially on asymmetries between treated and nontreated breast (3–5). These methods do not take into account the global appearance of aesthetic results, failing to include other aspects such as scar appearance and differences in color between breasts (6). The adoption of a lower number of classes for evaluation of aesthetic results of breast cancer conservative treatment seems logical. A more sophisticated and less prone to interobserver variability results was undertaken by Cardoso et al., who developed a software that showed greater consensus regarding comparison (7). A study found differences in cosmetic outcome evaluation in breast reconstruction using transverse rectus abdominis myocutaneous flap and radiotherapy depending on the gender and the medical discipline of the observer (8). We would desire a more detailed description of the way of evaluation. b) Fibrosis was diagnosed clinically by breast examinations. The authors do not specify if the assessment was carried out by the same physician or, if there was an initiative to standardize the evaluation criteria. This would be recommended, as there may be large inter observer variability on scoring of breast fibrosis (8). Some authors have stimulated a more quantitative and less subjective appreciation of fibrosis, namely by the use of the tissue compliance meter (9).
WHAT IS THE TARGET VOLUME FOR PREOPERATIVE ACCELERATED PARTIAL BREAST IRRADIATION (APBI)? IN REGARDS TO NICHOLS ET AL. (INT J RADIAT ONCOL BIOL PHYS 2010;77:197–202) AND PALTA ET AL. (INT J RADIAT ONCOL BIOL PHYS 2010, IN PRESS)
Finally, the authors say that previous studies did not associate the tamoxifen use to the increase in complications or worse cosmetic results. We disagree. Collette et al. (10), studying 3,624 patients treated on the EORTC trial 22881-10882 ‘‘boost versus no boost,’’ generated a nomogram to forecast the long-term risk of breast fibrosis. Cox regression models assigned points to: age, occurrence of postoperative hematoma or edema, use of tamoxifen if premenopausal, concomitant chemotherapy, radiation quality, and type of boost.
To the Editor: Two recent studies have suggested preoperative accelerated partial breast irradiation (APBI) as an alternative to conventional, post-lumpectomy APBI (1, 2). We commend the authors’ efforts in this potentially important area of research, and we hope the following comments regarding target definition will be considered in future studies. To generate pre- and postoperative clinical target volumes (CTVs) for comparison, both studies used a 15-mm margin to expand both the preoperative gross tumor volume (GTV) and the postoperative surgical cavity. It seems to us that the margin used to expand a preoperative GTV should be larger than that used to expand a lumpectomy cavity. As summarized in a recent publication, a 15-mm tumor bed-to-CTV margin, ‘‘is based upon data from mastectomy studies which suggest that 90% of subclinical multifocal and multicentric disease lies within 30 mm of the edge of index tumour. If, on average, the index tumour is excised with a margin of around 15 mm, a further 15 mm TB–CTV margin might reasonably be expected to encompass the majority of sub-clinical disease’’ (3). Whether a 30-mm CTV margin should actually be used for preoperative APBI is open to debate. A recent study suggests, for example, that a smaller margin could be considered for tumors without an extensive intraductal component (4). Nevertheless, to use the same margin pre- and postoperatively seems arguable. If a larger margin is used preoperatively,
CARLOS G.B. LIMA, JR., M.D. ARNO L. CORDOVA, JR., M.D. HENRIQUE BALLONI, M.D. Department of Radiation Oncology Oncoville, Clinic, Curitiba CARLOS G.B. LIMA, JR., M.D. ERNANI L. DE S THIAGO, M.D. ARNO L. CORDOVA, JR., M.D. Brazil Breast Cancer Department Radiotherapy Sao Sebastiao Florianopolis, Brazil doi:10.1016/j.ijrobp.2010.11.006 1. Murphy C, Anderson PR, Li T, et al. Impact of the radiation boost on outcomes after breast-conserving surgery and radiation. Int J Radiat Oncol Biol Phys 2010. Epub August 9, 2010.
314
Letters to the Editor then the conclusion that irradiated volumes will be smaller compared with conventional APBI may not hold. When constructing their planning target volume (PTVs), both studies excluded the first 5 mm under the skin surface, and one study excluded tissue beyond the posterior boundary of the breast. We believe the PTV, which accounts for setup error and intrafraction motion, should not be trimmed in this fashion. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39 protocol is explicit on this point. We appreciate the dose calculation and optimization issues, but a CTV located superficially or near the chest wall still requires consideration of setup error and breathing motion in those directions. Some dose–volume histogram parameters for target coverage are assessed using a trimmed volume. However, we believe that interplan comparisons of irradiated volume and skin dose should involve an untrimmed PTV. Preoperative imaging and/or treatment for APBI present a worthy subject for research, with promise of greater confidence in target definition and localization. We look forward to seeing further work in this area. LEONARD KIM, M.S., A.MUS.D. SIMONA SHAITELMAN, M.D., ED.M. Department of Radiation Oncology William Beaumont Hospital Royal Oak, MI doi:10.1016/j.ijrobp.2010.12.038 1. Palta M, Yoo S, Adamson JD, et al. Preoperative single fraction partial breast radiotherapy for early-stage breast cancer. Int J Radiat Oncol Biol Phys 2010. Epub, Nov. 17, 2010. 2. Nichols EM, Dhople AA, Mohiuddin MM, et al. Comparative analysis of the post-lumpectomy target volume versus the use of pre-lumpectomy tumor volume for early-stage breast cancer: implications for the future. Int J Radiat Oncol Biol Phys 2010;77:197–202. 3. Kirby AM, Evans PM, Nerurkar AY, et al. How does knowledge of threedimensional excision margins following breast conservation surgery impact upon clinical target volume definition for partial-breast radiotherapy? Radiother Oncol 2010;94:292–299. 4. Schmitz AC, van den Bosch MAAJ, Loo CE, et al. Precise correlation between MRI and histopathology—exploring treatment margins for MRI-guided localized breast cancer therapy. Radiother Oncol 2010;97: 225–232.
IN RESPONSE TO DRS. KIM AND SHAITELMAN To the Editor: We appreciate the opportunity to respond to Drs. Kim and Shaitelman regarding the definition of appropriate target volumes in preoperative partial-breast irradiation. From a surgical perspective, the aim of wide local excision is removal of tumor with a 1- to 2 cm margin of grossly normal tissue (1). In reality, this rarely translates to large, uniform microscopic margins. Instead, margins tend to be anisotropic, with tumor often approaching one or more margins quite closely (2, 3) (Fig. 1). Thus, the 1.5 cm expansion on the postoperative tumor bed likely provides a great deal more than a 30-mm margin on the original tumor in some areas and a great deal less in others. Although we agree that the appropriate preoperative margin is unclear, we would argue that a small portion of the postoperative treatment volume yields the majority of effect in reducing local recurrence, whereas the remainder treats normal tissue with little clinical benefit.
Fig. 1. Illustration of postoperative (left) and preoperative (right) partial-breast irradiation volumes. Red: gross tumor volume; blue: surgical excision volume; white: clinical target volume.
315
In addition, imaging capabilities have evolved markedly since Holland’s seminal work suggesting that subclinical disease was primarily contained within 30 mm of the index lesion. In a detailed microscopic evaluation of lumpectomy specimens, 93% of patients had no subclinical invasive disease 10 mm beyond the edge of the lesion visible on MRI (4). In contrast, ductal carcinoma in situ was present beyond 10 mm in 33%, but this dropped to 16% at 15 mm and 5% at 20 mm. Although the tumor characteristics in this population were heterogeneous, our protocol is limited to carefully selected patients with biologically favorable disease, who fall largely within the category of patients deemed ‘‘suitable’’ for accelerated partial-breast irradiation (5). As a result, we hypothesize that margins in the range of 1.5–2 cm will provide the best balance of target and normal tissue coverage. We agree with the authors that the planning target volume (PTV) expansion is important in accounting for setup error and intrafraction motion. We used a PTV margin of 3 mm, although the skin (first 3 mm of subcutaneous tissue) was subtracted from the PTV when relevant. Admittedly, this PTV is significantly less than that used in the National Surgical Adjuvant Breast and Bowel Project B-39 protocol. However, because of the single-fraction nature of this treatment, we believe that a larger PTV may not be necessary. In addition, we have incorporated fiducial markers, on-board kilovoltage imaging, and mild patient sedation in order to minimize errors due to treatment positioning and motion. This is an area of evolving research, and we appreciate the authors’ comments. We look forward to continued discussion towards optimizing this approach. MANISHA PALTA, M.D. JANET K. HORTON, M.D. Department of Radiation Oncology Duke University Medical Center Durham, NC doi:10.1016/j.ijrobp.2010.12.036 1. Gennaro M, Ferrais C, Guida V, et al. Conservative surgery in breast cancer. Significance of resection margins. Breast 2001;10:432–437. 2. Kirby AM, Evans PM, Nerurkar AY, et al. How does knowledge of threedimensional excision margins following breast conservation surgery impact upon clinical target volume definition for partial-breast radiotherapy? Radiother Oncol 2020;94:292-299. 3. Hanbeukers B, Borger J, Van den Ende P, et al. Customized computed tomography-based boost volumes in breast-conserving therapy: Use of three-dimensional histological information for clinical target volume margins. Int J Radiat Onol Biol Phys 2009;75:757– 763. 4. Schmitz AC, van den Bosch MAAJ, Loo CE, et al. Precise correlation between MRI and histopathology—exploring treatment margins for MRI-guided localized breast cancer therapy. Radiother Oncol 2010;97: 225–232. 5. Smith BD, Arthur DW, Buchholz TA, et al. Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). Int J Radiat Oncol Biol Phys 2009;74: 987–1001.
IN RESPONSE TO DRS. KIM AND SHAITELMAN To the Editor: We respectfully disagree with the comments by Drs. Kim and Shaitelman regarding the need for larger margins to cover microscopic tumor extension. It is true that surgeons typically try to take a cuff of normal tissue between 5 and 15 mm around the gross tumor to ensure negative microscopic margins. The flaw of this comment is the inherent lack of precision of surgery. This is demonstrated by the lack of benefit from the addition of MRI to reduce the re-excision rates after a lumpectomy due to inadequate margins, as well as by the fact that CT imaging rarely underestimates the pathologic size unless there is a noninvasive component of the disease (1, 2). Last, in the era of stereotactic body radiotherapy, it is common practice not to add any margin to cover microscopic tumor extension because it is thought that a dose sufficient to control microscopic disease will treat a cuff of normal tissue up to 1 cm away. An example of this is described in the recently published TARGIT-A trial, which prescribed a single dose of 20 Gy to the surface of the lumpectomy cavity with 5–7 Gy present at 1-cm depth. This study showed equivalent local control between the two cohorts at 4 years (3).
LETTERS TO THE EDITOR 2. Harris JR, Levene MB, Svensson G, et al. Analysis of cosmetic results following primary radiation therapy for stages I and II carcinoma of the breast. Int J Radiat Oncol Biol Phys 1979;5:257–261. 3. Pezner RD, Patterson MP, Hill LR, Vora N, Desai KR, Archambeau JO, et al. Breast retraction assessment: An objective evaluation of cosmetic results of patients treated conservatively for breast cancer. Int J Radiat Oncol Biol Phys 1985;11:575–578. 4. Tsouskas LI, Fentiman IS. Breast compliance: a new method for evaluation of cosmetic outcome after conservative treatment of early breast cancer. Breast Cancer Res Treat 1990;15:185–190. 5. van Limbergen E, van der Schueren E, van Tongelen K. Cosmetic evaluation of breast conserving treatment for mammary cancer. 1. Proposal of a quantitative scoring system. Radiother Oncol 1989;16:159–167. 6. Triedman SA, Osteen R, Harris JR. Factors influencing cosmetic outcome of conservative surgery and radiotherapy for breast cancer. Surg Clin North Am 1990;70:901–916. 7. Cardoso MJ, Cardoso J, Amaral N, et al. Turning subjective into objective: The BCCT core software for evaluation of cosmetic results in breast cancer conservative treatment. The Breast 2007;16: 456–461. 8. Leonardi MC, Garusi C, Santoro L, et al. Impact of the medical discipline and observer gender on cosmetic outcome evaluation in breast reconstruction using transverse rectus abdominis myocutaneous (TRAM) flap and radiotherapy. J Plast Reconstr Aesthet Surg 2000 Dec;63(12): 2091–2097. 9. Wernicke AG, Parashar B, Kulidzhanov F, et al. Prospective study validating inter- and intraobserver variability of tissue compliance meter in breast tissue of healthy volunteers: Potential implications for patients with radiation-induced fibrosis of the breast. Int J Radiat Oncol Biol Phys. 2010;80:39–46. 10. Collette S, Collette L, Budiharto T. Predictors of the risk of fibrosis at 10 years after breast conserving therapy for early breast cancer: A study based on the EORTC Trial 22881–10882 ‘boost versus no boost’. Eur J Cancer 2008;44:2587–2599. Erratum in Eur J Cancer 2009;45:2061.
IMPACT OF THE RADIATION BOOST ON OUTCOMES AFTER BREAST-CONSERVING SURGERY AND RADIATION: IN REGARD TO MURPHY C, ET AL. (INT J RADIAT ONCOL BIOL PHYS IN PRESS) To the Editor: We have read with profound interest the article by Murphy et al., ‘‘Impact of the radiation boost on outcomes after breast-conserving surgery and radiation’’ (1). The authors are commended for pointing out that a boost is not always necessary in all patients. We have found, however, a few points that deserve consideration. a) The cosmetic result after radiotherapy was scored by the 4-point scale (2). The most usual method using the Harvard scale is subjective as it evaluates a patient’s appearance on a photograph and has frequently used personnel involved in the treatment process for this purpose. The objective methods use measurements taken from the patient or from photographs, and are based essentially on asymmetries between treated and nontreated breast (3–5). These methods do not take into account the global appearance of aesthetic results, failing to include other aspects such as scar appearance and differences in color between breasts (6). The adoption of a lower number of classes for evaluation of aesthetic results of breast cancer conservative treatment seems logical. A more sophisticated and less prone to interobserver variability results was undertaken by Cardoso et al., who developed a software that showed greater consensus regarding comparison (7). A study found differences in cosmetic outcome evaluation in breast reconstruction using transverse rectus abdominis myocutaneous flap and radiotherapy depending on the gender and the medical discipline of the observer (8). We would desire a more detailed description of the way of evaluation. b) Fibrosis was diagnosed clinically by breast examinations. The authors do not specify if the assessment was carried out by the same physician or, if there was an initiative to standardize the evaluation criteria. This would be recommended, as there may be large inter observer variability on scoring of breast fibrosis (8). Some authors have stimulated a more quantitative and less subjective appreciation of fibrosis, namely by the use of the tissue compliance meter (9).
WHAT IS THE TARGET VOLUME FOR PREOPERATIVE ACCELERATED PARTIAL BREAST IRRADIATION (APBI)? IN REGARDS TO NICHOLS ET AL. (INT J RADIAT ONCOL BIOL PHYS 2010;77:197–202) AND PALTA ET AL. (INT J RADIAT ONCOL BIOL PHYS 2010, IN PRESS)
Finally, the authors say that previous studies did not associate the tamoxifen use to the increase in complications or worse cosmetic results. We disagree. Collette et al. (10), studying 3,624 patients treated on the EORTC trial 22881-10882 ‘‘boost versus no boost,’’ generated a nomogram to forecast the long-term risk of breast fibrosis. Cox regression models assigned points to: age, occurrence of postoperative hematoma or edema, use of tamoxifen if premenopausal, concomitant chemotherapy, radiation quality, and type of boost.
To the Editor: Two recent studies have suggested preoperative accelerated partial breast irradiation (APBI) as an alternative to conventional, post-lumpectomy APBI (1, 2). We commend the authors’ efforts in this potentially important area of research, and we hope the following comments regarding target definition will be considered in future studies. To generate pre- and postoperative clinical target volumes (CTVs) for comparison, both studies used a 15-mm margin to expand both the preoperative gross tumor volume (GTV) and the postoperative surgical cavity. It seems to us that the margin used to expand a preoperative GTV should be larger than that used to expand a lumpectomy cavity. As summarized in a recent publication, a 15-mm tumor bed-to-CTV margin, ‘‘is based upon data from mastectomy studies which suggest that 90% of subclinical multifocal and multicentric disease lies within 30 mm of the edge of index tumour. If, on average, the index tumour is excised with a margin of around 15 mm, a further 15 mm TB–CTV margin might reasonably be expected to encompass the majority of sub-clinical disease’’ (3). Whether a 30-mm CTV margin should actually be used for preoperative APBI is open to debate. A recent study suggests, for example, that a smaller margin could be considered for tumors without an extensive intraductal component (4). Nevertheless, to use the same margin pre- and postoperatively seems arguable. If a larger margin is used preoperatively,
CARLOS G.B. LIMA, JR., M.D. ARNO L. CORDOVA, JR., M.D. HENRIQUE BALLONI, M.D. Department of Radiation Oncology Oncoville, Clinic, Curitiba CARLOS G.B. LIMA, JR., M.D. ERNANI L. DE S THIAGO, M.D. ARNO L. CORDOVA, JR., M.D. Brazil Breast Cancer Department Radiotherapy Sao Sebastiao Florianopolis, Brazil doi:10.1016/j.ijrobp.2010.11.006 1. Murphy C, Anderson PR, Li T, et al. Impact of the radiation boost on outcomes after breast-conserving surgery and radiation. Int J Radiat Oncol Biol Phys 2010. Epub August 9, 2010.
314
Letters to the Editor then the conclusion that irradiated volumes will be smaller compared with conventional APBI may not hold. When constructing their planning target volume (PTVs), both studies excluded the first 5 mm under the skin surface, and one study excluded tissue beyond the posterior boundary of the breast. We believe the PTV, which accounts for setup error and intrafraction motion, should not be trimmed in this fashion. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39 protocol is explicit on this point. We appreciate the dose calculation and optimization issues, but a CTV located superficially or near the chest wall still requires consideration of setup error and breathing motion in those directions. Some dose–volume histogram parameters for target coverage are assessed using a trimmed volume. However, we believe that interplan comparisons of irradiated volume and skin dose should involve an untrimmed PTV. Preoperative imaging and/or treatment for APBI present a worthy subject for research, with promise of greater confidence in target definition and localization. We look forward to seeing further work in this area. LEONARD KIM, M.S., A.MUS.D. SIMONA SHAITELMAN, M.D., ED.M. Department of Radiation Oncology William Beaumont Hospital Royal Oak, MI doi:10.1016/j.ijrobp.2010.12.038 1. Palta M, Yoo S, Adamson JD, et al. Preoperative single fraction partial breast radiotherapy for early-stage breast cancer. Int J Radiat Oncol Biol Phys 2010. Epub, Nov. 17, 2010. 2. Nichols EM, Dhople AA, Mohiuddin MM, et al. Comparative analysis of the post-lumpectomy target volume versus the use of pre-lumpectomy tumor volume for early-stage breast cancer: implications for the future. Int J Radiat Oncol Biol Phys 2010;77:197–202. 3. Kirby AM, Evans PM, Nerurkar AY, et al. How does knowledge of threedimensional excision margins following breast conservation surgery impact upon clinical target volume definition for partial-breast radiotherapy? Radiother Oncol 2010;94:292–299. 4. Schmitz AC, van den Bosch MAAJ, Loo CE, et al. Precise correlation between MRI and histopathology—exploring treatment margins for MRI-guided localized breast cancer therapy. Radiother Oncol 2010;97: 225–232.
IN RESPONSE TO DRS. KIM AND SHAITELMAN To the Editor: We appreciate the opportunity to respond to Drs. Kim and Shaitelman regarding the definition of appropriate target volumes in preoperative partial-breast irradiation. From a surgical perspective, the aim of wide local excision is removal of tumor with a 1- to 2 cm margin of grossly normal tissue (1). In reality, this rarely translates to large, uniform microscopic margins. Instead, margins tend to be anisotropic, with tumor often approaching one or more margins quite closely (2, 3) (Fig. 1). Thus, the 1.5 cm expansion on the postoperative tumor bed likely provides a great deal more than a 30-mm margin on the original tumor in some areas and a great deal less in others. Although we agree that the appropriate preoperative margin is unclear, we would argue that a small portion of the postoperative treatment volume yields the majority of effect in reducing local recurrence, whereas the remainder treats normal tissue with little clinical benefit.
Fig. 1. Illustration of postoperative (left) and preoperative (right) partial-breast irradiation volumes. Red: gross tumor volume; blue: surgical excision volume; white: clinical target volume.
315
In addition, imaging capabilities have evolved markedly since Holland’s seminal work suggesting that subclinical disease was primarily contained within 30 mm of the index lesion. In a detailed microscopic evaluation of lumpectomy specimens, 93% of patients had no subclinical invasive disease 10 mm beyond the edge of the lesion visible on MRI (4). In contrast, ductal carcinoma in situ was present beyond 10 mm in 33%, but this dropped to 16% at 15 mm and 5% at 20 mm. Although the tumor characteristics in this population were heterogeneous, our protocol is limited to carefully selected patients with biologically favorable disease, who fall largely within the category of patients deemed ‘‘suitable’’ for accelerated partial-breast irradiation (5). As a result, we hypothesize that margins in the range of 1.5–2 cm will provide the best balance of target and normal tissue coverage. We agree with the authors that the planning target volume (PTV) expansion is important in accounting for setup error and intrafraction motion. We used a PTV margin of 3 mm, although the skin (first 3 mm of subcutaneous tissue) was subtracted from the PTV when relevant. Admittedly, this PTV is significantly less than that used in the National Surgical Adjuvant Breast and Bowel Project B-39 protocol. However, because of the single-fraction nature of this treatment, we believe that a larger PTV may not be necessary. In addition, we have incorporated fiducial markers, on-board kilovoltage imaging, and mild patient sedation in order to minimize errors due to treatment positioning and motion. This is an area of evolving research, and we appreciate the authors’ comments. We look forward to continued discussion towards optimizing this approach. MANISHA PALTA, M.D. JANET K. HORTON, M.D. Department of Radiation Oncology Duke University Medical Center Durham, NC doi:10.1016/j.ijrobp.2010.12.036 1. Gennaro M, Ferrais C, Guida V, et al. Conservative surgery in breast cancer. Significance of resection margins. Breast 2001;10:432–437. 2. Kirby AM, Evans PM, Nerurkar AY, et al. How does knowledge of threedimensional excision margins following breast conservation surgery impact upon clinical target volume definition for partial-breast radiotherapy? Radiother Oncol 2020;94:292-299. 3. Hanbeukers B, Borger J, Van den Ende P, et al. Customized computed tomography-based boost volumes in breast-conserving therapy: Use of three-dimensional histological information for clinical target volume margins. Int J Radiat Onol Biol Phys 2009;75:757– 763. 4. Schmitz AC, van den Bosch MAAJ, Loo CE, et al. Precise correlation between MRI and histopathology—exploring treatment margins for MRI-guided localized breast cancer therapy. Radiother Oncol 2010;97: 225–232. 5. Smith BD, Arthur DW, Buchholz TA, et al. Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). Int J Radiat Oncol Biol Phys 2009;74: 987–1001.
IN RESPONSE TO DRS. KIM AND SHAITELMAN To the Editor: We respectfully disagree with the comments by Drs. Kim and Shaitelman regarding the need for larger margins to cover microscopic tumor extension. It is true that surgeons typically try to take a cuff of normal tissue between 5 and 15 mm around the gross tumor to ensure negative microscopic margins. The flaw of this comment is the inherent lack of precision of surgery. This is demonstrated by the lack of benefit from the addition of MRI to reduce the re-excision rates after a lumpectomy due to inadequate margins, as well as by the fact that CT imaging rarely underestimates the pathologic size unless there is a noninvasive component of the disease (1, 2). Last, in the era of stereotactic body radiotherapy, it is common practice not to add any margin to cover microscopic tumor extension because it is thought that a dose sufficient to control microscopic disease will treat a cuff of normal tissue up to 1 cm away. An example of this is described in the recently published TARGIT-A trial, which prescribed a single dose of 20 Gy to the surface of the lumpectomy cavity with 5–7 Gy present at 1-cm depth. This study showed equivalent local control between the two cohorts at 4 years (3).