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In Reply

Sunnybrook Health Sciences Centre, Toronto, Canada

Ivo Olivotto

BC Cancer Agency, Vancouver Island Centre, Canada

Dr Vordermark raises important points regarding the dose prescription and volume definition for breast intensity-modulated radiotherapy (IMRT) that must be put into context. Current breast IMRT techniques are the result of a long technical evolution, starting with the introduction of computed tomography planning that highlighted the poor dose distribution homogeneity within the breast when using physical wedges. A single institution cohort study suggested that breast IMRT reduces acute skin toxicity compared with wedges¹ and a randomized trial demonstrated that breast IMRT improved cosmetic outcomes.² Our study provided further evidence that the wide adoption of breast IMRT was clinically justified.³ In our study, the dose prescription and the target volume definition were identical between arms and were consistent with standard practice in North America.^1,4 Random assignment resulted in equivalent breast volumes between the treatment arms as measured by bra size, volume receiving 95% of the prescribed dose, or breast separation. The breast IMRT technique resulted in improved dosimetry, the most noticeable improvement was the elimination of the hot-spot in the inframammary fold, and this improvement translated into a significantly reduced occurrence of moist desquamation.

Vordermark contends that "advanced radiotherapy planning and delivery techniques such as IMRT require precise definitions." This is correct, but one must also be practical. Many volume definitions and constraints required during IMRT planning used for improving dose distribution conformality are pointless for techniques like breast IMRT where the aim is to improve dose homogeneity. Manually contouring the breast slice-by-slice will not improve the dose distribution but will result in a more cumbersome, time-consuming, and less cost-effective planning process.

Most authors reporting on breast IMRT define the planning target volumes as the irradiated volume encompassing the breast and chest wall covered by the opposed tangential beams, excluding the lung and the skin layer.^1,4 The skin layer is excluded because electronic equilibrium is not met and planning systems have substantial uncertainty about dose within 5 to 6 mm of the skin-air interface. The 95% isodose is a convenient cutoff to define the posterior portion of the planning target volumes and was used as a surrogate for the breast volume in our multivariable analysis. Whether the breast clinical target volume should include the skin is debatable. To the best of our knowledge, there is no report of an increased risk of breast recurrence if the skin is underdosed. The several techniques in use for accelerated partial breast irradiation all avoid skin irradiation and have not reported higher skin recurrence rates. Similarly, the concept that the skin should be clearly defined as an organ at risk and therefore used in the dose optimization process is not supported by our trial data. In our randomized study, breast IMRT improved dose homogeneity so efficiently that fewer patients required the use of mixed 6/18 MV energy beams compared with the standard wedge arm (19.4% v 51.5%; P < .001, respectively). Because mixed energy beams reduce the dose to the skin, this should have resulted in an increased incidence of skin toxicity in the IMRT arm. This increased incidence was not observed, suggesting that the dose to the skin surface is not the only cause of radiation-induced acute skin toxicity.

While reviewing each plan for quality assurance purposes, we got the sense that the physiopathology of moist desquamation may be a more complex phenomenon than just due to dose overexposure of the skin. The hot-spots often occurred well beneath the skin surface, and the larger they were, the more severe the skin reactions observed. It is possible that radiation-induced moist desquamation could be as much the result of significant subcutaneous inflammation rather than just a pure skin burn. If so, defining the skin as an organ at risk would have a limited impact on skin toxicity prevention, while our trial shows that improving the dose distribution throughout the breast volume has a favorable impact on skin toxicity.

Whether a two opposite beam breast IMRT technique needs to include margins for organ motion and set-up error is also debatable. As for standard breast tangents, the photon field is extended 1.5 to 2 cm anteriorly into air and the posterior limit is inside the lung due to the shape of the breast. Extending these margins further would not improve the dose distribution.

We appreciate Dr Vordermark's correspondence and hope this debate will facilitate the translation of our randomized trial findings into the practice of modern breast cancer radiation therapy.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Vicini FA, Sharpe M, Kestin L, et al: Optimizing breast cancer treatment efficacy with intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 54:1336-1344, 2002[CrossRef][Medline]

2. Donovan E, Bleakley N, Denholm E, et al: Randomised trial of standard 2D radiotherapy (RT) versus intensity modulated radiotherapy (IMRT) in patients prescribed breast radiotherapy. Radiother Oncol 82:254-264, 2007[CrossRef][Medline]

3. Pignol JP, Olivotto I, Rakovitch E, et al: A multicenter randomized trial of breast intensity-modulated radiation therapy to reduce acute radiation dermatitis. J Clin Oncol 26:2085-2092, 2008[Abstract/Free Full Text]

4. Donovan EM, Yarnold JR, Adams EJ, et al: An investigation into methods of IMRT planning applied to breast radiotherapy. Br J Radiol 81:311-322, 2008[Abstract/Free Full Text]

Related Correspondence

• Skin-Sparing Intensity-Modulated Radiotherapy of the Breast
  Dirk Vordermark
  JCO 2008 26: 3292 [Full Text]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Google Scholar Articles by Pignol, J.-P. Articles by Olivotto, I. PubMed PubMed Citation Articles by Pignol, J.-P. Articles by Olivotto, I. Related Articles Related Correspondence