Journal of Cancer Research and Therapeutics Medknow Publications on behalf of the Association of Radiation Oncologists of India (AROI) ISSN: 0973-1482 EISSN: 1998-4138 Vol. 4, Num. 3, 2008, pp. 126-130

Journal of Cancer Research and Therapeutics, Vol. 4, No. 3, July-September, 2008, pp. 126-130

Original Article

Normal tissue complication probability of fibrosis in radiotherapy of breast cancer: Accelerated partial breast irradiation vs conventional external-beam radiotherapy

Jothy Basu KS, Bahl Amit, Subramani V, Sharma DN, Rath GK, Julka PK

Department of Radiation Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi-110 029
Correspondence Address:Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi-110 029
dramitbahl@yahoo.com

Code Number: cr08037

Abstract

Keywords: Accelerated partial breast irradiation, breast, normal tissue complication probability

Introduction

Breast -conserving treatment involving whole breast radiotherapy is a well-accepted treatment modality in women presenting with early-stage breast cancer. ^[1],[2] However, concerns over long-term cosmetic, cardiac, and pulmonary toxicity are increasingly being debated. As treatment techniques become more refined, the focus on cosmetic outcome is increasing. Fibrosis is one of the important long-term sequelae seen in irradiated breasts using conventional tangential fields and has an significant impact on the cosmesis and quality of life of the patients. A grade III-IV fibrosis of 10-16% has been seen in patients on longer follow-up. ^[3] Using limited radiotherapy fields is one way of decreasing this treatment-related morbidity. Conformal radiotherapy techniques like intensity-modulated radiotherapy (IMRT) has been shown to reduce chronic breast edema after treatment. ^[4] However, an increase in late normal tissue toxicity has also been reported using IMRT in breast cancer treatment due to a larger volume of tissue receiving sub-prescription doses. ^[5] Accelerated partial breast irradiation (APBI) appears to be another promising modality for reduction of chronic treatment-related effects. ^[6] APBI treatment can be delivered either by brachytherapy using mammosite or interstitial techniques or with external-beam radiotherapy using conformal portals.

Though dosimetric comparison of different techniques used to deliver APBI have been reported, none of these studies have used normal tissue complication probability (NTCP) modeling to quantify post-treatment fibrosis. ^[7] NTCP models can help us predict the expected long-term fibrosis in treated patients and help compare different treatment techniques. In this dosimetric study we have used the relative-seriality model to predict NTCP for fibrosis in treated breasts using APBI delivered with conformal 3D external-beam technique and whole-breast conventional tangential treatments followed by electron boost.

Materials and Methods

Ten postoperative early-stage breast cancer cases (T1N0M0) were included in this dosimetric study. CT images of all the cases were acquired with a slice thickness of 2.5 mm with the patient immobilized in the treatment position. The lumpectomy cavity was identified with the help of surgical clips. EclipseT (Varian Associates, Palo Alto, CA) treatment-planning system was used for contouring and planning. A uniform margin of 2 cm was given to the gross tumor volume (GTV) to clinical target volume (CTV) and a uniform margin of 1 cm was given to the CTV to planning target volume (PTV). The target volume outside or close to the skin was removed with a skin-to-target margin of 5 mm. To calculate the NTCP of the ipsilateral breast fibrosis we subtracted the target volume from the normal breast tissue using Boolean functions available in the treatment planning system and named it normal ipsilateral breast tissue (NIBT). A detailed description of the treatment planning and radiobiological model used in the study is given below.

Treatment planning
All the conventional initial-phase and APBI treatment plans were planned using 6 MV photons. The conventional treatment comprised an initial-phase treatment followed by a boost treatment with electron beam to the primary tumor. The initial-phase treatment was planned using conventional photon tangential fields with SSD (source-to-skin distance) technique. The field parameters such as field weight, wedge angle, and collimator angle were chosen so as to achieve maximum coverage and dose uniformity in the region of interest. The boost treatment was planned with electrons in the energy range of 9-16 MeV, depending upon the target coverage and dose uniformity achievable for the selected patient. The prescription doses were 50 Gy in 25 fractions for the initial-phase and 16 Gy in 8 fractions for the boost-phase. The field arrangements are shown in [Figure 1a] and [Figure 1b].

APBI treatment was planned with a combination of five coplanar and non-coplanar beams with 6 MV photons with isocentric technique. Wedges were used wherever necessary to increase the dose uniformity. The prescription isodose level was chosen such that at least 95% of the target volume would receive the prescription dose. The prescription dose was 38 Gy in 10 fractions for the APBI treatment. The field arrangements are shown in [Figure 2a] and [Figure 2b].

NTCP model
The NTCP model used in this study is entirely based on the model fitting parameters calculated by Alexander et al . and the relative-seriality model proposed by Kallman et al . ^[8] The relative-seriality model, which is based on the Poisson model of cell survival, gives the probability P(D, v) of cell death when a fractional volume v is given a dose D [Equation 1]:

Where γ is the slope of the dose-response curve at 50% response and D ₅₀ is the dose to cause a given effect in 50% of the population. In this we have replaced D by equivalent uniform dose (EUD) and D ₅₀ by EUD ₅₀ . EUD ₅₀ is 62.4 Gy in conventional fractionation as calculated by Alexander et al . Using this probability model the NTCP is calculated as follows:

Where s describes the hybrid serial/parallel architecture of the organ, a large value of s indicates a serial structure, and a small value indicates a parallel structure. An s value of 0.12 is used in this study as calculated by Alexander et al .

For the purpose of calculating EUD the dose matrices of the initial and boost phases were summed for the conventional treatment. The differential dose-volume histograms (DVH) of the NIBT were used to calculate the EUD with ′a′ value of 0.78 as calculated by Alexander et al ., using Equation 3 proposed by Niemeirko ^[9] :

Where v _i is the fractional volume irradiated to dose D _i , V _Total is the total volume of the structure, and ′a′ is the tissue-specific model fitting parameter.

For the APBI plans the individual voxel doses were converted to conventional fractionation doses using the classical biologically equivalent dose (BED) equation [Equation 4]; the voxel equivalent doses (VED) were then used to calculate the EUD for equivalent fractionation. ^[10]

Where D is the total dose delivered, d is the dose per fraction, and α/β is a tissue-dependant parameter. In this study, we used an α/β value of 3, as normal breast parenchyma behaves as late-reacting tissue.

Results

Discussion

Radiation-induced fibrosis is influenced by a number of factors like age, nutritional status, coexisting morbidity, surgery, and biological differences between patients. Radiotherapy-related factors can also play a major role in determining the extent of fibrosis. Cosmetic outcome is important in breast-conserving treatment, and doses above 50 Gy used in whole-breast radiotherapy are known to be associated with a poor cosmetic outcome. ^[11] Our study has shown the superiority of APBI delivered by 3D conformal radiotherapy over conventional treatment in reducing radiation-induced fibrosis in ipsilateral breast. APBI using 3D conformal radiotherapy has been shown to be almost equivalent to multicatheter brachytherapy and mammosite brachytherapy in terms of EUD and tumor control probability. ^[12] Alexander et al . have analyzed NTCP for fibrosis in breast, comparing IMRT with conventional treatment methods. Their results showed increased NTCP with IMRT treatments due to increased dose to areas receiving sub-prescription doses.

APBI is expected to reduce breast fibrosis more than conventional whole-breast radiotherapy; however, there are very few studies that have attempted to calculate the NTCP for breast fibrosis, probably due to lack of radiobiological model fitting parameters. We have attempted to quantify the fibrosis complication probability in APBI and conventional treatment. Such radiobiological models will be of great help for designing individualized treatments for patients and also to assess the prescription dose. Even though these radiobiological models are highly dependant on the model fitting parameters, it can be used to compare plans where the relative difference is less likely to be affected by input parameters.

However, an APBI treatment protocol needs to be carefully implemented. Delineation of the lumpectomy cavity can be a source of error. APBI treatments should not be attempted unless the lumpectomy cavity can be clearly identified with the help of surgical clips placed at the time of surgery. The issue of organ motion also needs to be addressed. Using image-guided radiotherapy or an active breathing coordinator may be a way out. In the absence of such sophisticated equipment, a slightly larger PTV can be taken to compensate for respiratory motion. Many of these issues call for a larger randomized study to be undertaken.

Conclusions

References

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