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Originally published as JCO Early Release 10.1200/JCO.2006.09.1041 on April 30 2007 © 2007 American Society of Clinical Oncology. Phase I-II Trial of Prone Accelerated Intensity Modulated Radiation Therapy to the Breast to Optimally Spare Normal Tissue
From the Department of Radiation Oncology, Division of Biostatistics; and the Department of Surgery, New York University Cancer Institute and New York University School of Medicine, New York, NY Address reprint requests to Silvia C. Formenti, MD, New York University School of Medicine, THI98, 566 First Ave, New York, NY 10016; e-mail: silvia.formenti{at}med.nyu.edu
Purpose To report the clinical feasibility of a trial of accelerated whole-breast intensity modulated radiotherapy, with the patient in prone position, optimally to spare the heart and lung.
Patients and Methods Patients with stages I or II breast cancer, excised by breast conserving surgery with negative margins, were eligible for this institutional review board–approved prospective trial. Computed tomography simulation was performed with the patient prone on a dedicated breast board, in the exact position used for treatment. A dose of 40.5 Gy, delivered at 2.7 Gy in 15 fractions, was prescribed to the index breast with an additional concomitant boost of 0.5 Gy delivered to the tumor bed, for a total dose of 48 Gy to the lumpectomy site. Physics constraints consisted of limiting Results Between September 2003 and August 2005, 91 patients were enrolled on the study. Median length of follow-up was 12 months (range, 1 to 28 months). In all patients the technique was feasible and heart and lung sparing was achieved as prescribed by the protocol. Acute toxicities consisting mostly of reversible grades 1-2 skin dermatitis (67%) and fatigue (18%) occurred in 75 patients. One patient sustained a regional recurrence rapidly followed by distant metastases. Conclusion Accelerated whole breast intensity modulated radiotherapy in the prone position is feasible and it permits a drastic reduction in the volume of lung and heart tissue exposed to significant radiation.
The last National Institutes of Health Consensus Development Conference statement on adjuvant therapy in breast cancer, in 2000, maintained whole-breast radiotherapy (RT) is the standard complement to breast conservation surgery.1 Standard whole-breast RT is generally delivered over 6 weeks, with treatment sessions daily, 5 days per week. Adherence to this protocol is often a challenge, especially among elderly patients.2-4 The exploration of shorter (accelerated), biologically equivalent, treatment regimens is warranted and it is feasible through dose hypofractionation.5,6 A radiobiological algorithm is available to convert standard fractionation to hypofractionation, based on the prediction that a larger dose per fraction given over a shorter period of time is as effective as the more traditional longer schedule, provided that consideration is given to the risk of long-term complications derived by the use of larger radiation fractions.7-10 A recently completed Canadian phase III prospective randomized trial compared conventional whole-breast radiation fractionation to accelerated hypofractionated RT for node-negative early stage breast cancer patients, after lumpectomy. The study demonstrated the equivalence between 42.5 Gy in 16 fractions over 22 days and the standard 50 Gy in 25 fractions regimen over 35 days: survival, local control, and cosmetic results were comparable between the two arms, with 5 years of follow-up.11 With the latest advances in radiation technology, such as the development of new radiation techniques including intensity-modulated RT, doses can be delivered to the breast more homogeneously, while sparing the normal tissues.12-15 Furthermore, through our previous work funded by a grant from the Department of Defense Breast Cancer Research Program (DAMD17-01-1-0345, 2001-2004), we acquired invaluable experience in delivering RT to the breast with patients in the prone position.16,17 The main advantages of prone positioning are a better exclusion of the heart and lung from the radiation fields and reduced respiratory movement.18,19 We designed a dedicated breast radiation mattress, lined with memory foam, that facilitates comfortable prone positioning (Fig 1). As the breast falls by force of gravity away from the chest through an opening in the mattress, heart and lung tissues can be excluded from radiation beams. Figure 2 shows a typical example of a patient on study who had undergone imaging with supine and prone set-up. The computed tomography cut included in the upper corner of each digital radiograph (Figs 2A and B) corresponds to the plane identified by the same reference radio-opaque markers (originally placed by the clinician to define the medial and lateral extent of the breast when supine). Noticeably, the tumor bed also changes in shape and distance from the chest wall, depending on the setup. The prone position enables the inclusion of the target breast in the tangential opposed RT fields while excluding the heart and lung from the beam's eye view.
This sparing of critical normal tissue is even more important in light of the several emerging reports about a correlation between breast irradiation and the risk of cardiovascular and pulmonary toxicities.20-23,25,26 Moreover, modern adjuvant trials incorporate potentially cardiotoxic agents27 with the risk of a compounded morbidity among recipients of left breast RT.28,29 Therefore, to both spare normal tissue and shorten the course of whole-breast RT, we designed an accelerated radiation regimen, 15 fractions over 3 weeks, maintaining the same targets of conventional breast RT (entire index breast, with a boost to the tumor bed) but with the patient planned and treated in the prone position.30,31 Based on radiobiological modeling, we selected a dose likely to have comparable morbidity to that of a standard 6-week regimen and explored the use of intensity-modulated RT (IMRT) to enable treating the whole breast with a concomitant boost to the tumor bed. Table 1 describes the study design.
The primary objectives of the trial were to assess feasibility, achieve normal tissue sparing, test the long-term efficacy of this approach, and to explore the cosmetic outcome of a concomitant boost with IMRT. The secondary end point was to prospectively collect blood specimens to perform radiation genomic studies, to assess DNA polymorphisms and their associations with RT-induced long-term cosmetic outcomes, and to explore markers predictive of late radiation sequelae, such as fibrosis, retraction, and telangiectasia.32-34 This report focuses on the clinical feasibility of the study, while the dosimetric results and physical discussion of this approach are described separately.35-37
Patient Eligibility Previously untreated pre- or postmenopausal women with stage I and II invasive breast cancer, excised with negative margins, were eligible to this protocol after segmental mastectomy and sentinel node biopsy and/or axillary node dissection (for tumors < 5 mm in pathologic size no nodal assessment was required). Patients were excluded if more than three nodes were found to be involved at axillary dissection because they would require treatment with an axillary and supraclavicular field. Carriers of active connective tissue disorders were also excluded. For patients undergoing adjuvant chemotherapy, a minimum interval of 2 weeks from the last chemotherapy course was required before starting RT. The maximum allowed interval from previous cancer therapy (either surgery or chemotherapy) was 8 weeks. Toxicity was assessed by Radiation Therapy Oncology Group and Late Effects on Normal Tissues (LENT)/Subjective, Objective, Management and Analytic (SOMA) criteria.38
Radiobiological Rationale for Dose Selection
Patient Set-Up and Physics Methods The treatment volume was determined according to field borders established with the patient in the supine position and visualized on computed tomography images through the use of radio-opaque markers. These fiducials were used to construct volumetric boundaries for contouring the breast tissue. With the patient laying prone, additional triangulation fiducials were added to the chest and on the lateral aspect of the breast to enable daily reproducibility of the treatment setup (Fig 2B). The first planning target volume (PTV1) consisted of the volume of the breast defined by the fiducials after shrinking the surface borders of this nominal breast tissue by 5 mm. This reduction accounted for penumbra and buildup effects associated with conventional breast tangent fields. The second planning target volume (PTV2) was constructed by adding a 1-cm margin to the defined tumor bed to account for patient setup. The PTV2 was restricted to be within PTV1 and as such also excluded regions considered outside of the body or within the build-up region or within the volume of lung or heart.
Beams energies between 4 MV and 10 MV were allowed. Multibeam arrangements were used to design plans to treat the whole breast (PTV1) to a daily fraction dose of 2.7 Gy, with the tumor bed region (PTV2) boosted by an additional 0.5 Gy, using IMRT. The goals of planning were to deliver a concomitant boost to the tumor bed and to minimize the size of the 3.2 Gy volumes outside of PTV2 while maintaining
Statistical Considerations
Between September 2003 and August 2005, 91 patients were enrolled on the study. One subject revoked her consent to participate and thus has been excluded from the analysis. Summaries of baseline patient and tumor characteristics for 90 patients are provided in Table 3. Median age at the time of consent was 57.2 years (range, 28.6 to 80.9 years). Median length of follow-up was 12 months (range, 1 to 28.7 months).
Eligibility to the protocol had no restrictions regarding patient size or breast size. The proposed technique was feasible in all patients accrued.
There were no treatment breaks because of acute toxicity. Most importantly, the physical constraints for normal tissue were readily observed in all cases: Follow-up information is available for all 90 patients enrolled. Toxicities consisted mainly of skin dermatitis (67.6%), as shown in Table 4. Only two patients had grade 3 acute toxicity, (one in skin and one with fatigue). One or more reportable late toxicities occurred in 60 of 84 patients who had at least one follow-up visit after 90 days from enrollment into the study (Table 4). There were no grade 3 late toxicities.
In this series, each of the 30 women with either pathologically involved nodes (18 patients) or other risk factors that warranted systemic treatment (12 patients) underwent chemotherapy before entering the trial. In 17 of 30 patients chemotherapy consisted of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel, with one of five patients with HER2/neu overexpressing tumors also treated with concurrent trastuzumab, during the taxane component. The remaining 13 patients received standard cyclophosphamide, methotrexate, and fluorouracil or doxorubicin and cyclophosphamide adjuvant treatment. One of 90 treated patients on this protocol sustained a local regional recurrence, rapidly followed by distant metastasis. Diagnosed with stage IIB, pT2 N1miM0 infiltrating ductal carcinoma of the left breast, this patient had a 3-mm micrometastasis in the sentinel node. None of the 31 nodes removed by level I and II axillary dissection were involved. She underwent a dose-dense doxorubicin and cyclophosphamide followed by paclitaxel and adjuvant radiation to the breast, per protocol. Eight months after completion of RT, the patient presented with brachial plexopathy and a palpable mass in the left infra and supraclavicular region, pathologically confirmed by needle biopsy. Chemotherapy with taxotere and liposomal doxorubicin was administered for several cycles until she progressed with a new metastasis at the L5 vertebral body. After vertebrectomy with spinal stabilization, she was treated by RT to two sites: L3-S1, 45 Gy at 1.8 Gy per fraction and a left axillary and supraclavicular field, by IMRT, 46 Gy at 2 Gy per fraction, during bevacizumab, achieving excellent palliation of brachial plexopathy and back pain.
The Canadian trial by Whelan et al11 inspired us to test whether it is feasible and safe to extend the benefit of an accelerated whole-breast IMRT planned RT to a subset of breast cancer patients with a higher risk of local recurrence (ie, to include stage II patients and carriers of breast cancers with extensive intraductal component).48 Because of this wider eligibility criteria, and in view of emerging data of dose-dependence for local control at the site of the tumor bed,49 we elected to add an additional dose at the site of tumor excision, by using IMRT to treat the whole breast with a concomitant boost. Based on radiobiological modeling, we selected a regimen that would provide biologic effective dose equivalence to that of standard 6-week RT. While long-term follow-up is required to demonstrate efficacy and acceptability of late toxicity, the results presented demonstrate the feasibility of this approach. All patients accrued could be treated by this technique, and we found high set-up reproducibility by using a system of skin fiducial lead markers and a dedicated breast RT mattress that enabled comfortable prone lying during treatment. Acute toxicity encountered by the patients in this trial was quite modest, mainly restricted to grade 1 to 2 dermatitis. While the pattern of acute toxicity encountered appeared to be acceptable, it is much too early to adequately assess late toxicities. A particular concern regards the risk of breast fibrosis, especially among patients whose volume of the concomitant boost was occupying more than 25% of the ipsilateral breast tissue.34 Because one of the study aims was blood sampling collection for radiogenomic studies, it enabled future assessment of specific polymorphisms associated with a predisposition to parenchimal fibrosis after radiation damage. If the degree and rate of late toxicities are acceptable, this shorter regimen, much more convenient to the patient than the traditional 6 weeks, could be easily implemented at any RT facility equipped with IMRT. The technique used in this study deliberately missed draining lymph nodes. Eligibility to this trial was limited to women requiring breast irradiation, without inclusion of the draining axillary nodes. Compared with the supine set-up, recognized to assure only partial inclusion of axillary nodes,50,51 the prone technique provides even less coverage.52 This is of particular concern among patients who have undergone an inadequate axillary dissection or had a single sentinel node removed and found to contain microscopic metastases. In these patients, this approach may be inadequate. Longer follow-up is necessary to assess the regional recurrence risk, particularly among the 18 patients with positive nodes. Computed tomography planning enabled accurate determination of dose volume histograms, with a particular focus on heart and lung.53 This study did not compare the dosimetry results of IMRT in prone versus supine position, neither did it compare prone IMRT to prone two-dimensional or three-dimensional planned RT. Nevertheless, to our knowledge the reported dose estimates to lung and heart compare favorably with other strategies previously proposed to reduce or exclude the heart from the field of radiation in women with left breast cancer.54-56 We are currently conducting a prospective trial to study the role of positioning, by simulating and planning each patient twice, prone and supine. The position that best reduces heart and lung dose is chosen for treatment. Preliminary results from this trial demonstrate a superiority for prone set-up in the majority of patients.57 While the risk of cardiac death after adjuvant RT appears to decrease when modern cohorts of women are studied,58-60 a follow-up in excess of 20 years is required to adequately assess cardiovascular risk.20 The insufficient length of follow-up makes it impossible to draw definite conclusions with regard to more recently treated women. Radiation-induced cardiac damage can be visualized by single-photon emission computed tomography–gated myocardial perfusion scans. In one study, new perfusion defects were detected in 27% of patients as early as 6 months after RT, and their incidence reached 42% at 2 years. A strong correlation between these changes and the volume of the left ventricle included in the radiation field was demonstrated, with an incidence of 57% if more than 10% of the left ventricle was included in the beam's eye view, compared with 20% if less than 5% of the left ventricle was included.25 These findings confirmed the results from two European groups.61-63,64 Excluding the heart from the field of radiation, as achieved in this trial, will prevent these changes from occurring. Another late morbidity of breast RT concerns the increased risk of lung cancer, especially among smokers.50 The United States Surveillance, Epidemiology and End Results cancer registries have reported an increase in lung cancer deaths after RT and the 20-year hazards of breast RT regimens used in the 1970s and early 1980s are now apparent.65 In the United States Surveillance, Epidemiology and End Results cancer registry cohort reported by Darby et al, mortality from ipsilateral lung cancer was increased in comparison with mortality from contralateral cancer, supporting a dose-dependence effect. Measures to minimize lung exposure are likely to decrease the risk of secondary cancers.20 In conclusion, a commitment to maximal normal tissue sparing is warranted and it justifies our approach of meticulous avoidance of heart and lung by treating most breast cancer patients in the prone position. This approach, however, does not prevent the exposure of normal tissue outside the field to low doses generated by scattered radiation—future studies will elucidate the risk associated with such exposure.66 In the meantime, it remains the duty of radiation oncologists to continue to explore how to maximally reduce late morbidities of breast RT while maintaining its proven role in reducing breast cancer mortality.65 Similar efforts are warranted to identify regimens that converge efficacy with patients' convenience and quality of life.
The authors indicated no potential conflicts of interest.
Conception and design: Silvia C. Formenti, Judith D. Goldberg, Keith J. DeWyngaert Administrative support: Silvia C. Formenti, Daniel F. Roses Provision of study materials or patients: Silvia C. Formenti, Daniela Gidea-Addeo, Daniel F. Roses, Amber Guth, Barry S. Rosenstein, Keith J. DeWyngaert Collection and assembly of data: Silvia C. Formenti, Amber Guth Data analysis and interpretation: Silvia C. Formenti, Judith D. Goldberg, Daniel F. Roses, Barry S. Rosenstein, Keith J. DeWyngaert Manuscript writing: Silvia C. Formenti, Barry S. Rosenstein Final approval of manuscript: Silvia C. Formenti, Judith D. Goldberg, Barry S. Rosenstein, Keith J. DeWyngaert
published online ahead of print at www.jco.org on April 30, 2007 Supported by Department of Defense Grant No. DAMD 17-01-1-0345 and a New York University Cancer Institute Core Grant. Presented in part in poster format at the 49th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, October 27-November 1, 2007, Los Angeles, CA. Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
1. National Institutes of Health Consensus Development Conference statement: Adjuvant therapy for breast cancer, November 1-3, 2000. J Natl Cancer Inst Monogr 30:5-15, 2001 2. Joslyn SA: Radiation therapy and patient age in the survival from early-stage breast cancer. Int J Radiat Oncol Biol Phys 44:821-826, 1999[CrossRef][Medline] 3. Hebert-Croteau N, Brisson J, Latreille J, et al: Compliance with consensus recommendations for the treatment of early stage breast carcinoma in elderly women. Cancer 85:1104-1113, 1999[CrossRef][Medline] 4. Truong MT, Hirsch AE, Formenti SC: Novel approaches to postoperative radiation therapy as part of breast-conserving therapy for early-stage breast cancer. Clin Breast Cancer 4:253-263, 2003[Medline] 5. Suh WW, Pierce LJ, Vicini FA, et al: A cost comparison analysis of partial versus whole-breast irradiation after breast-conserving surgery for early-stage breast cancer. Int J Radiat Oncol Biol Phys 62:790-796, 2005[CrossRef][Medline] 6. Baillet F, Housset M, Maylin C, et al: The use of a specific hypofractionated radiation therapy regimen versus classical fractionation in the treatment of breast cancer: A randomized study of 230 patients. Int J Radiat Oncol Biol Phys 19:1131-1133, 1990[Medline] 7. Barendsen GW: Dose fractionation, dose rate and iso-effect relationships for normal tissue responses. Int J Radiat Oncol Biol Phys 8:1981-1997, 1982[Medline] 8. Matthews JH, Meeker BE, Chapman JD: Response of human tumor cell lines in vitro to fractionated irradiation. Int J Radiat Oncol Biol Phys 16:133-138, 1989[Medline] 9. Thames HD, Bentzen SM, Turesson I, et al: Time-dose factors in radiotherapy: A review of the human data. Radiother Oncol 19:219-235, 1990[CrossRef][Medline] 10. Fowler J: The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radiol 62:679-694, 1989 11. Whelan T, MacKenzie R, Julian J, et al: Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. J Natl Cancer Inst 94:1143-1150, 2002 12. Horton JK, Halle JS, Chang SX, et al: Comparison of three concomitant boost techniques for early-stage breast cancer. Int J Radiat Oncol Biol Phys 64:168-175, 2006[CrossRef][Medline] 13. Mayo CS, Urie MM, Fitzgerald TJ: Hybrid IMRT plans–concurrently treating conventional and IMRT beams for improved breast irradiation and reduced planning time. Int J Radiat Oncol Biol Phys 61:922-932, 2005[CrossRef][Medline] 14. Goodman KA, Hong L, Wagman R, et al: Dosimetric analysis of a simplified intensity modulation technique for prone breast radiotherapy. Int J Radiat Oncol Biol Phys 60:95-102, 2004[CrossRef][Medline] 15. Fraass BA, Kessler ML, McShan DL, et al: Optimization and clinical use of multisegment intensity-modulated radiation therapy for high-dose conformal therapy. Semin Radiat Oncol 9:60-77, 1999[CrossRef][Medline] 16. Formenti SC, Truong MT, Goldberg JD, et al: Prone accelerated partial breast irradiation after breast-conserving surgery: Preliminary clinical results and dose-volume histogram analysis. Int J Radiat Oncol Biol Phys 60:493-504, 2004[CrossRef][Medline] 17. Formenti SC: External-beam partial-breast irradiation. Semin Radiat Oncol 15:92-99, 2005[CrossRef][Medline] 18. Griem KL, Fetherston P, Kuznetsova M, et al: Three-dimensional photon dosimetry: A comparison of treatment of the intact breast in the supine and prone position. Int J Radiat Oncol Biol Phys 57:891-899, 2003[CrossRef][Medline] 19. el-Fallah AI, Plantec MB, Ferrara KW: Ultrasonic measurement of breast tissue motion and the implications for velocity estimation. Ultrasound Med Biol 23:1047-1057, 1997[CrossRef][Medline] 20. Darby SC, McGale P, Taylor CW, et al: Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: Prospective cohort study of about 300,000 women in US SEER cancer registries. Lancet Oncol 6:557-565, 2005[CrossRef][Medline] 21. Van de Steene J, Vinh-Hung V, Cutuli B, et al: Adjuvant radiotherapy for breast cancer: Effects of longer follow-up. Radiother Oncol 72:35-43, 2004[CrossRef][Medline] 22. Prosnitz RG, Chen YH, Marks LB: Cardiac toxicity following thoracic radiation. Semin Oncol 32:S71-S80, 2005[CrossRef][Medline] 23. Prosnitz RG, Marks LB: Radiation-induced heart disease: Vigilance is still required. J Clin Oncol 23:7391-7394, 2005 24. Reference deleted by author. 25. Marks LB, Yu X, Prosnitz RG, et al: The incidence and functional consequences of RT-associated cardiac perfusion defects. Int J Radiat Oncol Biol Phys 63:214-223, 2005[CrossRef][Medline] 26. Recht A: Which breast cancer patients should really worry about radiation-induced heart disease–and how much? J Clin Oncol 24:4059-4061, 2006 27. Ng R, Better N, Green MD: Anticancer agents and cardiotoxicity. Semin Oncol 33:2-14, 2006[Medline] 28. Valagussa P, Zambetti M, Biasi S, et al: Cardiac effects following adjuvant chemotherapy and breast irradiation in operable breast cancer. Ann Oncol 5:209-216, 1994 29. Shapiro CL, Hardenbergh PH, Gelman R, et al: Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients. J Clin Oncol 16:3493-3501, 1998[Abstract] 30. Guerrero M, Li XA, Earl MA, et al: Simultaneous integrated boost for breast cancer using IMRT: A radiobiological and treatment planning study. Int J Radiat Oncol Biol Phys 59:1513-1522, 2004[CrossRef][Medline] 31. Lief EP, DeWyngaert J, Formenti SC: IMRT for concomitant boost to the tumor bed for breast cancer radiation therapy. Int J Radiat Oncol Biol Phys 57:S366, 2003 32. Andreassen CN, Alsner J, Overgaard M, et al: Prediction of normal tissue radiosensitivity from polymorphisms in candidate genes. Radiother Oncol 69:127-135, 2003[CrossRef][Medline] 33. Lymberis SC, Parhar PK, Katsoulakis E, et al: Pharmacogenomics and breast cancer. Pharmacogenomics 5:31-55, 2004[CrossRef][Medline] 34. Andreassen CN, Overgaard J, Alsner J, et al: ATM sequence variants and risk of radiation-induced subcutaneous fibrosis after postmastectomy radiotherapy. Int J Radiat Oncol Biol Phys 64:776-783, 2006[CrossRef][Medline] 35. Mitchell J, Rosenstein B, Remon S: Whole breast accelerated IMRT with concomitant boost–dosimetric results in 70 patients. Radiological Society of North America, 92nd Scientific Assembly and Annual Meeting, 353, Chicago, IL, November 26, 2006 36. deWyngaert J, Lymberis SC, MacDonald S: Accelerated IMRT with concomitant boost after breast-conserving therapy (BCT): Preliminary clinical results and dose volume histogram (DVH) analysis. Int J Radiat Oncol Biol Phys 60:S386-S387, 2004[CrossRef] 37. deWyngaert J, Jozsef G, Mitchell J: Accelerated Intensity modulated radiation therapy (AIMRT) to the breast in the prone position: Dosimetric results. Int J Radiat Oncol Biol Phys, in press 38. Hoeller U, Tribius S, Kuhlmey A, et al: Increasing the rate of late toxicity by changing the score? A comparison of RTOG/EORTC and LENT/SOMA scores. Int J Radiat Oncol Biol Phys 55:1013-1018, 2003[CrossRef][Medline] 39. Lea D, Catcheside DG: The mechanism of the induction by radiation of chromosome aberrations in Trasdescantia. J Genet 44:216-245, 1942[CrossRef] 40. Steel G, Deacon J, Duchesnea GM: The dose-rate effect in human tumour cells. Radiother Oncol 9:299-310, 1987[CrossRef][Medline] 41. Turesson I, Thames H: Repair capacity and kinetics of human skin during fractionated radiotherapy: Erythema, desquamation, and telangiectasia after 3 and 5 years follow-up. Int J Radiat Oncol Biol Phys 15:169-188, 1989 42. Thames H, Bentzen S, Turesson I, et al: Time-dose factors in radiotherapy: A review of the human data. Radiother Oncol 19:219-235, 1990[CrossRef][Medline] 43. Archambeau JO, Pezner R, Wasserman T: Pathophysiology of irradiated skin and breast. Int J Radiat Oncol Biol Phys 31:1171-1185, 1995[CrossRef][Medline] 44. Yamada Y, Ackerman I, Franssen E, et al: Does the dose fractionation schedule influence local control of adjuvant radiotherapy for early stage breast cancer? Int J Radiat Oncol Biol Phys 44:99-104, 1999[CrossRef][Medline] 45. Travis E, Tucker S: Isoeffect models and fractionated radiation therapy. Int J Radiat Oncol Biol Phys 13:283-287, 1987[Medline] 46. Stanton PD, Cooke TG, Forster G, et al: Cell kinetics in vivo of human breast cancer. Br J Surg 83:98-102, 1996[Medline] 47. Haustermans K, Fowler J, Geboes K, et al: Relationship between potential doubling time (Tpot), labeling index and duration of DNA synthesis in 60 esophageal and 35 breast tumors: Is it worthwhile to measure Tpot? Radiother Oncol 46:157-167, 1998[CrossRef][Medline] 48. Holland R, Connolly JL, Gelman R, et al: The presence of an extensive intraductal component following a limited excision correlates with prominent residual disease in the remainder of the breast. J Clin Oncol 8:113-118, 1990 49. Bartelink H, Horiot JC, Poortmans P, et al: Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N Engl J Med 345:1378-1387, 2001 50. Reznik J, Cicchetti MG, Degaspe B, et al: Analysis of axillary coverage during tangential radiation therapy to the breast. Int J Radiat Oncol Biol Phys 61:163-168, 2005[CrossRef][Medline] 51. Reed DR, Lindsley SK, Mann GN, et al: Axillary lymph node dose with tangential breast irradiation. Int J Radiat Oncol Biol Phys 61:358-364, 2005[CrossRef][Medline] 52. Alonso-Basanta M, MacDonald S, Lymberis S: Dosimetric comparisons of supine versus prone radiation: Implications on normal tissue toxicity. Int J Radiat Oncol Biol Phys 63:S182-S183, 2005[CrossRef] 53. Gyenes G, Gagliardi G, Lax I, et al: Evaluation of irradiated heart volumes in stage I breast cancer patients treated with postoperative adjuvant radiotherapy. J Clin Oncol 15:1348-1353, 1997 54. Chen MH, Chuang ML, Bornstein BA, et al: Impact of respiratory maneuvers on cardiac volume within left-breast radiation portals. Circulation 96:3269-3272, 1997 55. Krauss DJ, Kestin LL, Raff G, et al: MRI-based volumetric assessment of cardiac anatomy and dose reduction via active breathing control during irradiation for left-sided breast cancer. Int J Radiat Oncol Biol Phys 61:1243-1250, 2005[CrossRef][Medline] 56. Raj KA, Evans ES, Prosnitz RG, et al: Is there an increased risk of local recurrence under the heart block in patients with left-sided breast cancer? Cancer J 12:309-317, 2006[Medline] 57. Parhar PK, Constantine C, Racsa-Alamgir M: 1082: Preliminary Results of NYU 05-181, a Prospective Trial to Establish the Individual Optimal Positioning for Breast Radiotherapy. Int J Radiat Oncol Biol Phys 66:S177-S177, 2006 58. Patt DA, Goodwin JS, Kuo YF, et al: Cardiac morbidity of adjuvant radiotherapy for breast cancer. J Clin Oncol 23:7475-7482, 2005 59. Vallis KA, Pintilie M, Chong N, et al: Assessment of coronary heart disease morbidity and mortality after radiation therapy for early breast cancer. J Clin Oncol 20:1036-1042, 2002 60. Giordano SH, Kuo YF, Freeman JL, et al: Risk of cardiac death after adjuvant radiotherapy for breast cancer. J Natl Cancer Inst 97:419-424, 2005 61. Gyenes G, Fornander T, Carlens P, et al: Morbidity of ischemic heart disease in early breast cancer 15-20 years after adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 28:1235-1241, 1994[Medline] 62. Gyenes G, Fornander T, Carlens P, et al: Myocardial damage in breast cancer patients treated with adjuvant radiotherapy: A prospective study. Int J Radiat Oncol Biol Phys 36:899-905, 1996[CrossRef][Medline] 63. Gyenes G, Fornander T, Carlens P, et al: Detection of radiation-induced myocardial damage by technetium-99m sestamibi scintigraphy. Eur J Nucl Med 24:286-292, 1997[Medline] 64. Seddon B, Cook A, Gothard L, et al: Detection of defects in myocardial perfusion imaging in patients with early breast cancer treated with radiotherapy. Radiother Oncol 64:53-63, 2002[CrossRef][Medline] 65. Clarke M, Collins R, Darby S, et al: Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomised trials. Lancet 366:2087-2106, 2005[Medline] 66. Hall EJ: Intensity-modulated radiation therapy, protons, and the risk of second cancers. Int J Radiat Oncol Biol Phys 65:1-7, 2006[CrossRef][Medline] Submitted October 4, 2006; accepted March 12, 2007.
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
5% of the heart volume to receive 
18 Gy and 
/ß values of either 2 or 4 Gy, and is only slightly lower when a 10 Gy 
