Contemporary Surgery

Partial-breast irradiation:
Rating today’s evidence

Assistant Professor of Surgery, Mayo Medical School, Mayo Clinic

Assistant Professor of Surgery, Mayo Medical School

Multidisciplinary Breast fellow, Mayo Clinic, Rochester, MN

A 56-year-old woman with stage I infiltrating ductal carcinoma underwent breast conservation surgery. She had negative margins and her sentinel lymph nodes were negative. She lives in Hawaii and has limited access to a radiation treatment facility.

Accelerated partial breast irradiation (APBI) may be a good option for her. It concentrates the radiation to a partial volume of the breast over 1–2 weeks compared with the 6–7 weeks that conventional whole-breast irradiation (WBI) demands. Possible advantages of APBI include convenience, less toxicity, good cosmesis, and adequate local control.

  The promise of APBI

The principle of APBI is based on the rationale that most in-breast recurrences occur within centimeters of the original disease site. Although several PBI techniques are available, they all share the primary advantage of a shorter treatment schedule with improved convenience of treatment.

Early experience suggests APBI is a feasible treatment option for selected early breast cancer patients following breast-conserving surgery. However, this modality remains an investigational treatment with unknown long-term efficacy and complication rates until the current prospective trials mature. Whether APBI can truly deliver these promises is the subject of ongoing investigations. This article discusses the rationale for APBI, reviews the different techniques, and updates the prospective phase-III randomized trials.

Rationale for APBI

Over the last 20 years, prospective randomized trials have demonstrated that survival for breast conserving therapy, or BCT, (which is lumpectomy followed by radiation to the entire breast) was equivalent to mastectomy.^1-3 In the National Surgical Adjuvant Breast and Bowel Project (NSABP B-06 trial), women who had lumpectomy alone showed a local recurrence rate of 39% at 20 years. That decreased to 14% when radiotherapy was added.¹

Postlumpectomy radiotherapy significantly reduces the risk of recurrence in the region of the tumor bed. The region at highest risk for microscopic residual disease and for in-breast recurrence is within 1–2 cm of the surgical bed.⁴

Recurrence rates away from the tumor bed are similar after lumpectomy alone or followed by whole-breast radiotherapy.² Patients with new breast primaries have significantly better survival and lower metastasis rates than those with true recurrence. Treatment of the tumor bed can decrease the rate of local disease recurrence.⁵

Clinical and nonclinical influences

Factors the patient and physician must take into account when considering BCT versus mastectomy are daily access to a radiation facility for 5–6 weeks, transportation, geographic proximity, local toxicity, and employment status.^6,7 Their relevance may explain why many American women who are candidates for BCT do not have that treatment.

Patient compliance with radiation is critical for the success of BCT. Only 36% of patients in one center completed the course of therapy and clinical follow-up.⁸

Is APBI the answer?

If local recurrences occur predominantly in the tumor bed, can one reduce the volume of radiotherapy along with treatment time and toxicity? APBI decreases the time required for radiotherapy, potentially reduces toxicity, and possibly improves patient quality of life.

APBI differs from WBI in these ways:

• WBI involves administering a total dose of at least 50 Gy to the entire breast. This is usually delivered in 25 fractions of 2 Gy, 5 days a week, over approximately 6 weeks.

• APBI delivers radiation therapy to the lumpectomy cavity plus a 1–2-cm margin after breast-conserving surgery in the patient with early stage breast cancer. The radiotherapy is completed in 4–6 days rather than over several weeks.

  The four APBI techniques

Four techniques for APBI are available: interstitial brachytherapy, intracavitary brachytherapy, intraoperative radiotherapy, and 3D conformal radiotherapy.

  Interstitial brachytherapy

Multicatheter brachytherapy is the oldest form of partial-breast irradiation. This treatment places 15–25 small hollow catheters about 1–1.5 cm apart in the surgical bed intraoperatively or shortly after tumor excision. A template guides the transcutaneous catheter, thus allowing uniform placement.

Low-dose rate (LDR) brachytherapy uses 0.4–2 Gy/hr while high-dose rate brachytherapy (HDR) uses dose rates greater than 12 Gy/hr. Studies of HDR reported good cosmesis and recurrence rates of 2% and 2.5% at median follow-up of 65 months and 7 years, respectively.^9,10 Advantages of interstitial brachytherapy include:

• Good control of radiation administration with the ability to tailor the dosing.

• Limited toxicity to healthy tissues.

• Short treatment sessions each lasting as little as 10 minutes over 5 days.

Disadvantages of this approach include the sophisticated planning required as well as the risks of infection and scarring from multiple skin puncture sites.

  Intracavitary brachytherapy

Intracavitary brachytherapy offers technical simplicity. The devices may be placed intraoperatively or postoperatively. However, disadvantages of these modalities are infection, radiation dermatitis, and balloon conformation that may make it difficult to achieve adequate skin spacing to treat an asymmetric cavity.

Double-lumen catheter

In 2002, the FDA approved a balloon-tipped interstitial catheter for intracavitary brachytherapy (MammoSite Radiation Therapy System, Cytyc Corporation, Palo Alto, CA) (FIGURE 2).

This is a double-lumen catheter with a central lumen that accommodates a high-dose radiation source (usually Ir-192). The catheter is placed transcutaneously with ultrasound guidance into the lumpectomy cavity either during the lumpectomy or postoperatively. The catheter and balloon must be positioned precisely: the balloon-to-skin distance is greater than 7 mm; the balloon conforms to more than 90% of the lumpectomy surface; and symmetry exists between the balloon and the center shaft.

A registry trial of 1500 patients treated with the MammoSite device has reported ipsilateral breast recurrences in 1.2% with mean follow-up of 15 months, but the trial is ongoing until patients have completed 7-year follow-up.^10,11 Excellent or good cosmetic results have been reported in 93%, with an overall infection rate of 8% (5.3% was device-related).^10,11

Radiation dermatitis in study subjects correlated with the distance from the skin to the radiation device, with a rate of 19.7% in the group with device-to-skin distance of 7 mm or greater versus 64% in those with device-to-skin distance of 5–7 mm.¹² The device was explanted in 9% for suboptimal skin distance, positive margins, and irregular cavity.⁹

Expandable bundle device

Another intracavitary brachytherapy device is the Strut Adjusted Volume Implant, or SAVI (Cianna Medical, Inc, Aliso Viejo, CA) that received FDA clearance in 2006 (FIGURE 3A). This device consists of an expandable bundle of catheters that surround a central lumen, allowing multicatheter treatments with a single-entry approach. Delivery of radiation through individual catheters allows better contour and control of dosing. It combines the tissue-sparing dosimetry of interstitial brachytherapy with the single-entry ease of intracavitary balloon brachytherapy.

Continuous-exposure brachytherapy

A similar system, the ClearPath HDR device (North American Scientific, Inc, Chatsworth, CA), aims to address skin margin issues with the advantage of a continuous release form (FIGURE 3B). This device inserts I-125 strands to achieve continuous exposure, allowing the patient to return home during treatment. A fully shielded comfortable bra protects others in close contact with the patient.

  Intraoperative radiotherapy

This technique delivers a high single-fraction radiation dose directly to the tumor bed intraoperatively, immediately after removal of the neoplastic tissue (FIGURE 1). A radiation generator transportable to the operating suite delivers the single-fraction IORT. This modality is more popular in Europe than the United States.

The advantages of intraoperative radiotherapy are maximal treatment convenience for the patient and sparing of normal tissue. Disadvantages are the need for dosimetric quality assurance and dedicated equipment, and delivery of radiation without the benefit of pathologic confirmation.

IORT devices

Devices that provide mobile IORT include the Intrabeam (Carl Zeiss Surgical, Oberkochen, Germany) and the Mobetron System (Intraop Medical Corporation, Sunnyvale, CA).

The Intrabeam emits soft x-rays at 50 kV peak via a 3.2-mm-diameter probe that can be covered with different size applicators to match the cavity size. It delivers doses of 20 Gy at the surface of the applicator and 5 Gy at 1 cm over a 30-min period. The Mobetron emits MeV electrons via a collimator tube. A lead shield on the pectoralis fascia under the breast protects the lung.¹³

Electron intraoperative therapy (ELIOT) has been pioneered by Umberto Veronesi and colleagues in Milan, Italy.^13,14 This technique delivers a dose of 21 Gy over 3 minutes via a collimator placed in the operative field under direct vision.

Complications among the 921 patients Veronesi’s group treated included liponecrosis (4.2%), hematoma (1.3%), and mild fibrosis (2.6%). The local recurrence rate was 1.6%. Veronesi’s group is now conducting a prospective trial comparing BCT with conventional radiotherapy and BCT with ELIOT of 21 Gy.

  3D CRT

Three-dimensional conformal radiation therapy (3D CRT) is a noninvasive method of delivering APBI that requires computer planning and localizing techniques. This modality uses CT scanning to image the lumpectomy cavity and plan the target volume.⁶ Among the advantages 3D CRT offers are:

• Increased dose homogeneity.

• No need for catheter placement.

• Utilization of equipment already present in the radiation suite.

Two reports of 3D CRT have been published.^15,16 In the phase-I/II PBI trial of 95 patients, median follow-up at 10 months showed no observable effects of radiotherapy, no recurrences, and a 100% rating of good cosmesis.¹⁵

The Radiation Therapy Oncology Group (RTOG) study 0319, a phase I/II trial, showed the feasibility and reproducibility of delivering APBI via 3D CRT across multiple institutions.¹⁶ This study evaluated 58 patients with stage I or II invasive ductal carcinoma 3 cm in diameter or less with negative surgical margins. Each was treated with a total of 38.5 Gy in 10 fractions over 5 days.

  APBI concerns and contraindications

Investigators must address several concerns before APBI becomes widely used. Fore-most is the oncologic issue of local recurrence. Large-scale, longer-term follow-up is needed before the efficacy of APBI can be compared with WBI. Likewise, published data are limited on the long-term effects on cosmesis and local complications of acute and chronic toxicity, including fibrosis.

The studies that have been published have included patients with early stage disease, so only very early results regarding cosmesis and efficacy are available.^11,12 Also, controversies surround the use of APBI for ductal carcinoma in situ (DCIS). APBI treats a limited field, whereas DCIS can be multifocal.¹⁷

The operator applies the intraoperative radiation without knowledge of final pathology and margin status, and concerns persist about the increased risk of axillary recurrence if PBI is pursued without axillary treatment fields in patients with 1–3 positive axillary nodes.

Disclosure

The authors have no affiliations to disclose.

References

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