Radiotherapy options to treat breast cancer are increasing

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Radiation therapist Erin Hendrickson (left) and assistant supervisor Sarah Lowitz position patient Marianne Melillo for an accelerated radiation treatment.

Radiation therapy has transformed breast cancer treatment over the last 40 years by enabling women with small, early-stage tumors to opt for breast-conserving lumpectomies instead of mastectomies.

But conventional whole-breast radiation can be inconvenient, even impractical, for some women because it requires brief sessions Monday through Friday for about six or seven weeks. Logistical challenges force many early-stage patients to choose mastectomy, or to skip part of their prescribed course of radiation, studies have found.

Now, radiotherapy options are multiplying as oncologists strive to condense the therapy and make it safer for normal tissue without compromising cancer control.

Canada and Europe have led the way in developing these advances. The most studied technique delivers larger-dose, or "hypofractionated," whole-breast irradiation over three to four weeks, rather than six to seven.

A newer approach, called partial-breast irradiation, focuses just on the tissue around the lumpectomy cavity. The radiation is delivered twice daily for five days externally or from within the breast using radioactive beads.

Another innovation, called intraoperative radiation, delivers a single concentrated dose to the open lumpectomy bed during surgery.

"The good news is that most women who get diagnosed have early-stage disease, so they have choices," said Marisa Weiss, director of breast radiation oncology at Lankenau Medical Center and founder of breastcancer.org. "It's important for doctors to let women know there are options."

Of the 230,000 women diagnosed annually with invasive breast cancer, about 180,000 are suitable for lumpectomy and radiation, and about 65 percent of them choose that treatment, studies indicate.

During lumpectomy, surgeons remove a margin of healthy breast tissue along with the tumor to try to eliminate all cancer. Still, undetectable malignant cells may be left behind. Adding radiation reduces the chance of recurrence in the treated breast from 10 percent or more to about 5 percent, studies show. Long-term survival is equal to mastectomy results.

Ionizing radiation works by damaging cellular DNA, the genetic material that directs cell division. Malignant cells are particularly susceptible because they are rapidly dividing, but healthy tissue such as skin, bones, the heart, and lungs may also suffer harm that shows up days, months, or even years later.

Indeed, U.S. radiation oncologists have been slow to embrace hypofractionated radiotherapy - despite validation by high-quality studies in Canada and Britain - partly because of outdated concerns about higher rates of toxic effects, including breast hardening and skin shrinkage. Such adverse effects were common when the accelerated radiation course was pioneered in the 1970s, but improved technology and lower total radiation dosages have largely addressed these problems, said University of Pennsylvania radiation oncologist Gary Freedman.

"Radiation oncologists have been taught that acceleration is a really bad thing to do," Freedman said. "When I was in my residency in the 1990s, we were told, 'Don't do it. It's just socialized medicine trying to save money.' "

In 2011, American radiation oncology guidelines endorsed hypofractionation for patients over 50. Yet a recent Penn study coauthored by Freedman found only 35 percent of eligible women got the shorter course in 2013, up from 11 percent in 2008. In contrast, 71 percent of eligible women in Ontario, Canada, received it.

Another coauthor of the study, Penn ethicist and breast oncologist Ezekiel J. Emanuel, believes the payment structure also discourages the shorter course because radiation oncologists can bill more for doing more treatment. The study found abbreviating therapy reduced insurers' spending per patient from $31,640 to $28,747.

In any case, resistance may be fading as U.S. studies affirm the safety of the three- to four-week therapy. A study published in August by the University of Texas MD Anderson Cancer Center found women who received hypofractionated therapy had less toxicity - including breast pain, skin reddening, and tiredness - than those who got the longer course. Six months later, they reported less fatigue and less trouble meeting family needs.

Moreover, the Anderson study successfully used hypofractionation on women not included in U.S. guidelines: those who are obese, under age 50, or diagnosed with preinvasive cancer confined to the milk ducts, called ductal carcinoma in situ, or DCIS.

Penn already offers the shorter course to such women, said Freedman, who uses it with two-thirds of his lumpectomy patients.

One of them, Marianne Mellilo, 55, of Norwood, said, "I was surprised by how few side effects there were. A bit of skin redness; that's it."

For Heather Jordan, 38, of West Chester, the shorter course meant 15 fewer radiation sessions.

"It doesn't sound like a lot less, but I will tell you it's taxing emotionally, as well as physically," she said. "To condense this long journey in a way that wasn't going to do any harm was very attractive to me."

Whole-breast external radiation is tried and true, but research has shown the tissue in the vicinity of the original tumor - not the whole breast - is at high risk of recurrence. Partial-breast radiation was developed to target only that area of concern.

The targeted rays can be delivered externally. But the more common method, known as "brachytherapy," involves placing radioactive "seeds" within an inflatable balloon or tiny tubes that are implanted in the breast. The seeds are inserted twice a day, up to 10 minutes at a time, typically for five days.

"It can be challenging to have a balloon or other device hanging out of the breast, but you're done in a week," said Weiss at Lankenau.

In theory, limiting radiation to a targeted area could spare normal tissue, reducing side effects. But studies to date have been too small and have not followed patients long enough to assess the merits.

"So far, it looks pretty good, but not as good" as whole-breast radiation, Weiss said. "It has a higher recurrence rate and higher infection rate."

Penny R. Anderson, director of breast and gynecologic radiation oncology at Fox Chase Cancer Center, said partial-breast irradiation was "still considered experimental. And not every woman is a candidate, even if she has a small, early tumor."

Intraoperative radiation is an even more radical departure because the therapy is delivered in a single dose during surgery while the breast is open.

A major clinical trial done at 33 centers in 11 countries compared this one-shot approach to conventional whole-breast radiation. Last year, the researchers published the results, concluding intraoperative radiation was more convenient, less toxic, less expensive, and had a "noninferior" recurrence rate.

Critics have hotly debated that conclusion. They point out that 20 percent of women who got intraoperative radiation also got conventional therapy to compensate for aggressive features of their cancers that were discovered during the postoperative pathology lab analysis.

What's more, critics say, the median follow-up was too short - only three years - during which time 3.3 percent of the intraoperative therapy group had a recurrence, compared to 1.3 percent with standard radiation.

Still, the new approach may become an important alternative.

At the University of Virginia Health System, researchers are using powerful intraoperative CT imaging technology that enables them to better customize the radiation dose to fit the shape of the tumor cavity.

"Many patients are willing to take a slight increase in the risk of recurrence for much more convenience, comparable overall survival, and decreased radiation to normal tissues," said Shayna Showalter, a breast surgical oncologist at UVA. "The nice thing about intraoperative radiation is you have significantly less dosage to the skin, heart, and lungs."

That benefit was crucial for UVA School of Nursing professor Susan Kools, who was diagnosed with DCIS.

She has lupus, an autoimmune disease that makes her more vulnerable to the toxic effects of radiation. She was considering a mastectomy - "which seemed very extreme for a tiny early cancer," she said - when she learned of Showalter's study of intraoperative radiotherapy.

Though the lumpectomy and one-shot radiation left her with "bone-crushing fatigue," she bounced back within weeks.

"I'm grateful I had the option," Kools said. "If the data continue to be as positive, I hope it does become more accessible."

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