Breast Preserving Therapy with Single Fraction Intraoperative Radiotherapy

US Oncology Review, 2005;1(1):21-4 DOI:


The standard treatment for breast cancer patients desiring breast-conserving therapy is partial mastectomy followed by external beam (EB) whole breast radiotherapy (WBRT). Several randomized trials demonstrate that patients who undergo a partial mastectomy alone, and do not receive adjuvant WBRT, have at least a three-fold increase of in-breast recurrences compared with those who receive EBRT.1–4 Based on these randomized trial results, the 1990 National Institutes of Health (NIH) Consensus5 and the 2001 Consensus Conference6 concluded that breast-conserving surgery should be accompanied by WBRT.

Unfortunately, despite randomized clinical trial results and NIH Consensus Statements, Patterns of Care Studies from the US demonstrate increasing deviation from these recommendations.

Data from the Surveillance Epidemiology and End Results (SEER) registry demonstrate that the percentage of patients receiving appropriate breast-conserving therapy declined from 1983 to 1995.7 Barriers to appropriate RT treatment appear to be multifactorial including distance to RT centers, decreased socioeconomic status, insurance coverage, and older age.8–14 More convenient and less costly RT regimens may improve compliance with adjuvant therapy recommendations and allow more women to choose breast-conserving therapy.

Accelerated partial breast irradiation (APBI) is a potentially attractive way to significantly reduce the duration of time a patient spends on an RT treatment course. The vast majority of in-breast cancer recurrences occur in the same quadrant as the primary tumor, whereas non-tumor bed recurrences and new primaries in the contralateral breast occur with similar frequency in irradiated and nonirradiated patients, suggesting that the primary efficacy of RT in early-stage disease is due to the eradication of residual disease in the region of the tumor bed.3,15–18 The majority of tumors may therefore be controlled by RT delivered only to the region of the tumor bed, sparing the remainder of the breast. APBI options include interstitial catheter-based brachytherapy, endocavitary brachytherapy, threedimensional (3-D) conformal RT and intra-operative RT (IORT).19–21 This article will focus on the two IORT options currently being investigated—partial mastectomy followed by IORT and vice versa.

IORT Delivered Following a Partial Mastectomy
Veronesi et al. were the first to report IORT to treat the excised tumor bed with a single dose of RT delivered in the operating room (OR).22,23 Briefly, their technique is as follows.A standard sentinel node procedure is performed followed by a standard quadrantectomy down to the pectoralis major fascia with at least 1cm of grossly tumor-free surgical margins. The breast parenchyma is then detached from the overlying skin as well as the underlying pectoralis muscle for 3–4cm. An aluminum-lead disk is then positioned on the surface of the pectoralis muscle to prevent irradiation of the chest wall. The breast parenchyma is temporarily re-approximated over the metal disk and the thickness of the breast tissue is measured with a ruler at multiple locations. The average thickness is then used to calculate the radiation dose. Single fraction radiation is performed with a mobile, linear accelerator (LINAC). The irradiation tube is placed directly onto the re-approximated breast tissue with the skin protected by a moist gauze. Following irradiation, the metal disk is removed and definitive surgical closure is completed.

Two hundred and thirty-seven patients with clinical T1, N0 breast cancers were treated with a quadrantectomy and axillary sentinel node procedure.23 With a median follow-up of 19 months, four (1.7%) patients developed mild or severe posttreatment breast fibrosis. Furthermore, three (1.4%) patients have developed an ipsilateral breast cancer and two (1%) patients have developed a contralateral breast cancer.23 With short-term follow-up, IORT appears to have an acceptable cosmetic result, but longer follow-up is necessary before conclusions regarding efficacy can be made.

  1. Veronesi U, Luini A, Del Vecchio M et al., “Radiotherapy after breast-preserving surgery in women with localized cancer of the breast”, N. Engl. J. Med. (1993);328(22): pp. 1,587–1,591.
  2. Clark RM, Whelan T, Levine M et al., “Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: an update. Ontario Clinical Oncology Group”, J. Natl. Cancer Inst. (1996); 88(22): pp. 1,659–1,664.
  3. Liljegren G, Holmberg L, Bergh J et al.,“10-Year results after sector resection with or without postoperative radiotherapy for stage I breast cancer: a randomized trial”, J. Clin. Oncol. (1999);17(8): pp. 2,326–2,333.
  4. Fisher B, Anderson S, Redmond C K et al., “Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer”, N. Engl. J. Med. (1995);333(22): pp. 1,456–1,461.
  5. NIH consensus conference,“Treatment of early-stage breast cancer”, JAMA (1991);265(3): pp. 391–395.
  6. The National Institutes of Health Consensus Development Conference:Adjuvant Therapy for Breast Cancer. Bethesda, Maryland, USA, Proc. J. Natl. Cancer Inst. Monogr. (November 1–3 2000);30: pp. 1–152.
  7. Nattinger A B, Hoffmann R G, Kneusel R T et al., “Relation between appropriateness of primary therapy for early-stage breast carcinoma and increased use of breast-conserving surgery”, Lancet (2000);356(9236): pp. 1,148–1,153.
  8. Morrow M,White J, Moughan J et al.,“Factors predicting the use of breast-conserving therapy in stage I and II breast carcinoma”, J. Clin. Oncol. (2001);19(8): pp. 2,254–2,262.
  9. Hillner B E, McDonald M K, Penberthy L et al.,“Measuring standards of care for early breast cancer in an insured population”, J. Clin. Oncol. (1997);15(4): pp. 1,401–1,408.
  10. 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 (1999);85(5): pp. 1,104–1,113.
  11. Hebert-Croteau N, Brisson J, Latreille J et al.,“Variations in the treatment of early-stage breast cancer in Quebec between 1988 and 1994”, CMAJ (1999);161(8): pp. 951–955.
  12. Ballard-Barbash R, Potosky A L, Harlan L C et al.,“Factors associated with surgical and radiation therapy for early stage breast cancer in older women”, J. Natl. Cancer Inst. (1996);88(11): pp. 716–726.
  13. Riley G F, Potosky A L, Klabunde C N et al.,“Stage at diagnosis and treatment patterns among older women with breast cancer: an HMO and fee-for-service comparison”, JAMA (1999);281(8): pp. 720–726.
  14. Potosky A L, Merrill R M, Riley G F et al.,“Breast cancer survival and treatment in health maintenance organization and feefor- service settings”, J. Natl. Cancer Inst. (1997);89(22): pp. 1,683–1,691.
  15. Veronesi U, Marubini E, Mariani L et al., “Radiotherapy after breast-conserving surgery in small breast carcinoma: long-term results of a randomized trial”, Ann. Oncol. (2001);12(7): pp. 997–1,003.
  16. Clark R M,Wilkinson R H, Miceli P N, MacDonald W D,“Breast cancer. Experiences with conservation therapy”, Am. J. Clin. Oncol. (1987);10(6): pp. 461–468.
  17. Vicini F, Arthur D, Polgar C, Kuske R, “Defining the efficacy of accelerated partial breast irradiation: the importance of proper patient selection, optimal quality assurance, and common sense”, Int. J. Radiat. Oncol. Biol. Phys. (2003);57(5): pp. 1,210–1,213.
  18. Smith T E, Lee D,Turner B C et al.,“True recurrence vs. new primary ipsilateral breast tumor relapse: an analysis of clinical and pathologic differences and their implications in natural history, prognoses, and therapeutic management”, Int. J. Radiat. Oncol. Biol. Phys. (2000);48(5): pp. 1,281–1,289.
  19. Sarin R,“Partial-breast treatment for early breast cancer: emergence of a new a paradigm”, Nat. Clin. Prac. Oncol. (2005);2(1): pp. 40–47.
  20. Pawlik T M, Buchholz T A, Kuerer H M,“The biologic rationale for and emerging role of accelerated partial breast irradiation for breast cancer”, J.Am. Coll. Surg. (2004);199(3): pp. 479–492.
  21. Wallner P,Arthur D, Bartelink H et al.,“Workshop on partial breast irradiation: state of the art and the science”, Bethesda,MD, December 8–10 2002 J. Natl. Cancer Inst. (2004);96(3): pp. 175–184.
  22. Orecchia R, Ciocca M, Lazzari R et al., “Intraoperative radiation therapy with electrons (ELIOT) in early-stage breast cancer”, Breast (2003);12(6): pp. 483–490.
  23. Veronesi U, Gatti G, Luini A et al.,“Full-dose intraoperative radiotherapy with electrons during breast-conserving surgery”, Arch. Surg. (Chicago Ill 1960) (2003);138(11): pp. 1,253–1,256.
  24. Ollila D W, Klauber-DeMore N, Tesche L J et al., “Feasibility of Breast Preserving Therapy with Single Fraction In Situ Radiotherapy Delivered Intraoperatively”, Ann. Surg. (2005); in press.
  25. Albertini J J, Lyman G H, Cox C et al., “Lymphatic mapping and sentinel node biopsy in the patient with breast cancer [see comments] JAMA (1996);276(22): pp. 1,818–1,822.
  26. Thames H D Jr,Withers H R, Peters L J, Fletcher G H, “Changes in early and late radiation responses with altered dose fractionation: implications for dose-survival relationships”, Int. J. Radiat. Oncol. Biol. Phys. (1982);8(2): pp. 219–226.
  27. Matthews J H, Meeker B E, Chapman J D, “Response of human tumor cell lines in vitro to fractionated irradiation”, Int. J. Radiat. Oncol. Biol. Phys. (1989);16(1): pp. 133–138.
  28. Williams M V, Denekamp J, Fowler J F, “A review of alpha/beta ratios for experimental tumors: implications for clinical studies of altered fractionation”, Int. J. Radiat. Oncol. Biol. Phys. (1985);11(1): pp. 87–96.
  29. 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. (1999);44(1): pp. 99–104.