Novel Radiotherapy Techniques Expand Options for Breast Cancer Patients

Susan J. Hoover, MD, FACS

Associate Member

Center For Women’s Oncology

Moffitt Cancer Center

Those of us who have treated patients with breast cancer for any extended period of time can likely share anecdotes about watching the treatment of this disease evolve to levels many of us could only have imagined when we began practicing. One such noteworthy development in the last several years has been the popularization of breast conservation surgery and the advancement of radiation options that go hand in hand with it.

Yet amid this trend toward more minimally invasive techniques in the treatment of breast cancer, it is disappointing to see that some studies demonstrate that mastectomy rates are higher among patients who live far away from radiation centers.

Schroen et al¹ found a 40% mastectomy rate among women who lived less than 10 miles from a radiation center, but a 55% rate among patients who lived greater than 50 miles away from a center.¹

Additionally, even among women who have elected to undergo a lumpectomy and the required radiation therapy, it has also been shown that the greater the distance the patient lives from a radiation center, the lower the patient compliance rate is among those undergoing the radiation.

In another study, Athas et al² found that patients living less than 25 miles from a radiation facility surprisingly have only an 84% compliance rate with their treatment. The compliance level declined even further with increasing distance; only 42% of lumpectomy patients living >100 miles from a radiation facility actually completed the recommended course, thus leaving themselves at increased risk of breast cancer recurrence.

Strategies Aim to Shorten Regimens

A host of radiation therapy regimens are now available to help provide women interested in breast conservation the possibility of abbreviated treatments, thus giving some women the option to save their breasts in lieu of mastectomy.

These additional options for shorter courses of radiation are helping ensure radiation compliance and increasing feasibility of lumpectomy for some women. In addition to the gold standard of conventional whole-breast radiation, given over 6 weeks, the Moffitt Cancer Center has been offering appropriately selected candidates shorter courses of radiation after lumpectomy including hypofractionated whole-breast radiation therapy over 3 to 4 weeks, accelerated partial breast irradiation (APBI) over 1 week, and intraoperative radiation therapy (IORT) given in one treatment while the patient is still under anesthesia at time of lumpectomy.

With respect to the employment of APBI and IORT, it is recognized through multiple clinical trials that approximately 90% of the time, local recurrences after breast conservation therapy occur within the index quadrant of the breast, near the original tumor bed.

Hence, there is a platform for these more localized radiation treatments designed to focus the radiotherapy to the lumpectomy cavity, which is the area most likely to fail and form a recurrence. It has also been observed in studies that partial breast radiation therapies such as IORT lower the overall toxicity and burden of radiation by allowing the use of a lower dose of radiation administered in fewer fractions over a shorter period of time while sparing the rest of the breast and the surrounding organs the effects of radiation therapy.

Specifically, these therapies may also eradicate or reduce many of the possible side effects commonly seen with external-beam radiation therapy (EBRT), including:

• Skin irritation/pigmentation changes
• Breast tissue fibrosis
• Fatigue
• Heart and lung exposure
• Effects to the normal, healthy breast tissue

IORT Device Used at Moffitt

Moffitt has found success with the INTRABEAM® Radiotherapy device that is employed to deliver IORT. The system comes with several applicators of various sizes that are mounted on the x-ray source. The breast tissue is conformed around the applicator/x-ray source, and then 20 Gy in one fraction is delivered to the lumpectomy cavity for approximately 20 to 40 minutes, depending upon the size of the applicator.

The INTRABEAM was used internationally as part of the targeted intraoperative radiotherapy (TARGIT-A) trial comparing IORT with traditional whole breast EBRT. The TARGIT-A trial randomized 3451 women equally to IORT or EBRT, with the 5-year results for local control and overall survival published in The Lancet in February.³ The data showed that when IORT was given with lumpectomy, the 5-year local recurrence rate was similar to that of EBRT. Breast cancer mortality in the two groups was also similar IORT has allowed some women to undergo lumpectomy who otherwise would have chosen a mastectomy due to work situations, transportation issues, or personal/family circumstances that made travel to a radiation facility 5 days a week for 6 weeks difficult to execute. IORT allows them to choose a lumpectomy, if that is their surgical treatment of choice, without the worry of completing the necessary radiation that must follow a lumpectomy.

Patient Criteria Important

Although these are enticing options, it is key to emphasize that IORT and APBI are not for every patient with breast cancer. The American Society for Radiation Oncology (ASTRO) has published a consensus statement for APBI providing guidance for patient selection.⁴

“Optimal” candidates are defined as patients with these characteristics:

• 60 years old
• Tumor size <2 cm
• Surgical margins >2 mm
• Estrogen receptor—positive tumors
• Invasive ductal carcinoma histology
• Lymph node negative

“Cautionary” candidates are described with these characteristics:

• 50 to 59 years old
• Tumor size 2.1-3.0 cm
• Surgical margins <2 mm
• Estrogen receptor—negative tumors
• Invasive lobular carcinoma histology
• Pure ductal carcinoma in situ <3 cm

ASTRO has not yet developed guidelines for selecting patients with breast cancer for IORT therapy.⁵ At Moffitt, eligible candidates for INTRA- BEAM single-dose treatment include patients with small tumor size, negative excision margins, negative lymph nodes, and those who are postmenopausal age.

Since January 2011, Moffitt has treated more than 100 women with IORT. This technique has provided our patients with early-stage breast cancer an option that is state of the art, allowing many of them latitude in their surgical decision making with outcomes equivalent to more traditional radiation modalities.

It is vital to remember that application of such pioneering techniques as IORT requires a team approach of surgeons and radiation oncologists vigilantly selecting appropriate candidates to ensure translation to optimal outcomes and patient satisfaction.

Dr Hoover specializes in minimally invasive surgery techniques, incorporating sentinel lymph node biopsy, breast ultrasound, breast needle biopsy and accelerated partial breast irradiation into her patient care.

References

1. Schroen AT, Brenin DR, Kelly MD, Knaus WA, Slingluff CL Jr. Impact of patient distance to radiation therapy on mastectomy use in early-stage breast cancer patients. J Clin Oncol. 2005;23(28):7074-7080.
2. Athas WF, Adams-Cameron M, Hunt WC, Amir-Fazli A, Key CR. Travel distance to radiation therapy and receipt of radiotherapy following breast-conserving surgery. J Natl Cancer Inst. 2000;92(3):269-271.
3. Vaidya JS, Wenz F, Bulsara M, et al. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial [published online November 13, 2013]. Lancet. 2014; 383(9917):603-613.
4. Smith BD, Arthur DW, Buchholz TA, et al. Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). Int J Radiat Oncol Biol Phys. 2009;74(4):987-1001.
5. Guidelines: Breast Cancer. American Society for Radiation Oncology website. https://www.astro.org/Clinical-Practice/ Guidelines/Breast-Cancers.aspx. Updated July 11, 2014. Accessed October 19, 2014.