June 12, 2010 -- Delivering radiation to the tissues surrounding a breast cancer tumor immediately after it is removed now has the support of a positive clinical trial -- but doctors say much more proof is still needed before it can be considered anything but experimental.
The procedure is known by the acronym TARGIT -- short for targeted intraoperative radiation therapy. Doctors expose the tissues around the site of a tumor to a short period of radiation during breast-conserving surgery. The idea is to target the tissues that where the cancer has the highest risk of returning.
But breast cancer experts cited concerns about the low radiation dose used in the procedure, the relatively short follow-up in the clinical trial, and the expense of the equipment. Most said they would not offer the procedure outside of a clinical trial.
"It is way too early to draw solid conclusions in order to safely recommend targeted intraoperative radiotherapy to any group of patients based on these immature data," according to Dr. Henry Mark Kuerer of M.D. Anderson Cancer Center in Houston, Texas.
The data come from a large randomized trial that found the process to be at least as effective as standard radiation therapy.
The procedure could help patients avoid the lengthy and often difficult process of whole-breast radiation therapy by combining both lumpectomy and radiation in a single procedure, according to Jayant Vaidya of University College London. Vaidya was lead author on the study, published online in The Lancet and presented at the same time at the Chicago meeting of the American Society of Clinical Oncology.
They argued that the data are sufficiently strong that the process "should be considered as an alternative to external beam radiotherapy delivered over several weeks."
But most experts who responded to a query about the issue begged to differ.
The therapy "would be welcomed by women with early breast cancer," Kuerer said in an email to ABC News, but the data aren't yet strong enough. Specifically, he said, the average follow-up for patients was only two years, and fewer than 20 percent were followed for longer than four years.
"For breast cancer, this very short follow-up period is considered unacceptably small to draw conclusions about local recurrence," he said.
Indeed, the follow-up is so short, according to Dr. William Wood of Emory University in Atlanta, that the results remind him of the answer given by the man who had jumped from a skyscraper and was asked as he passed the 20th floor how he was enjoying the trip -- "exhilarating!"
TARGIT May Not Be Ready for Clinical Practice, Docs Warn
The current data, he said in an email, "are like that mythic interview" since problems would take 10 or more years to show up.
Dr. Len Lichtenfeld, deputy chief scientific officer for the American Cancer Society, also asked if the follow-up was adequate but told MedPage Today that's not the only issue with the study.
Lichtenfeld noted that two major centers -- contributing more than 500 patients to the 2,232-patient study -- were allowed to decide how to treat patients after their removed tumor had been tested pathologically.
That, he said, raises the "potential of selection bias" -- in other words, that some women who got the TARGIT treatment were selected because they would probably do well.
Indeed, Lichtenfeld said, most of the women in the study had favorable characteristics, making it difficult to know how widely the findings apply.
The TARGIT process is a subset of what is called partial-breast irradiation, which is itself still controversial. While many experts believe so-called accelerated PBI is valuable, most say they will remain cautious until the results of a definitive trial now under way are available.
With the TARGIT approach, at least three forms of accelerated PBI are being tested:
In TARGIT, the surface of the tumor bed is given a low dose of X-rays for between 20 and 35 minutes after the tumor is removed and before the wound is closed. No other radiation is intended to be given, although in the study 14 percent of women also got additional external beam radiation.
In 3-D conformal external beam radiation, beams of radiation are computer-guided to hit just the tissue that doctors think needs it. The radiation is typically delivered over five days.
In balloon brachytherapy, a small balloon is inflated to fit snugly in the space left by the tumor, connected with the surface of the breast with a catheter. Over a five-day period, a radioactive seed is placed in the balloon for a period of time each day to deliver the radiation.
Although all three remain experimental, many centers offer 3-D conformal external beam radiation or balloon brachytherapy when whole breast radiation for several weeks is difficult or impossible for women.
The difference, according to Dr. Jay Harris of Brigham and Women's Hospital in Boston, is that those approaches have "reasonable data" to support them. "Single intraoperative APBI does not," he said.
Some Medical Centers Considering TARGIT
Indeed, even when those approaches are offered, physicians are careful to counsel that they remain experimental.
The Moffitt Cancer center in Tampa uses both APBI approaches, according to radiation oncologist Dr. Eleanor Harris. Patients who seek either form are "counseled that APBI is not the standard of care, that there is a lack of long term outcome and toxicity data and that equivalent results to whole breast irradiation cannot be guaranteed," she said in an email.
Harris said the Lancet study "makes a strong case" for some patients to get the intra-operative therapy, but she also noted that "follow-up is short."
Moffitt currently doesn't have the equipment for the TARGIT approach, although it plans on getting it. On the other hand, Harris said, "the vast majority, if not all, patients" treated with the approach will be part of clinical trials.
Dr. Thomas Julian of Allegheny General Hospital in Pittsburgh said that current therapies successfully delay both local and systemic recurrences in early stage breast cancer, meaning that a short follow-up might not reveal differences in outcomes.
The TARGIT data is "premature," he said in an email, but the outcome of the NSABP study -- Julian is a senior official on the trial -- will "answer questions that will change standards of care."
"I am not ready to recommend PBI outside of a trial for routine therapy in place of [whole breast irradiation] until the long term outcome data are available," Julian said.
That opinion was not completely universal. Dr. Stefan Glück of the University of Miami's Leonard M. Miller School of Medicine, said in an email that he and radiation oncologists at his institution are prepared to recommend PBI, although he did not comment specifically on TARGIT.
And Dr. Susan Love of the Dr. Susan Love Research Foundation, said: "I do think these findings are practice-changing."
Love cautioned that the TARGIT approach needs specialized equipment that is not widely available, "which may limit its adoption" and she also noted the short follow-up.
But, she said, "for too long studies have just added more and more invasive surgery, radiation and chemotherapy. It is about time that we explored how we can also do less." Her foundation, based in Santa Monica, Calif., finances research into breast cancer.
Some experts worry that the relatively low dose used in the TARGIT approach may not be enough. Typically, external beam radiotherapy -- the current standard of care -- gives 40 to 56 Gray of radiation, often with a boost of another 10 of 15 Gray.
Low Radiation for Breast Cancer May Not Be Enough, Doctors Fear
In the TARGIT procedure, the surface of the tumor bed typically receives 20 Gray that attenuates to between five and seven Gray at a depth of one centimeter.
"We think that the dose of radiation used ... is rather low and we are concerned about the long term results," said Dr. Alphonse Taghian of Massachusetts General Hospital in Boston.
Taghian said his institution uses PBI "off protocol for a selected group of patients" but only with the 3-D conformal technique. They "would not use the intraoperative technique as described in the Lancet paper," he said in an email.
On the other hand, "use in selected patients now is rational, especially frail elderly patients with small, excellent-prognosis tumors," according to Dr. Larry Norton of Memorial Sloan-Kettering Cancer Center in New York city.
For most patients, though, it's still experimental, he said in an email, adding he would not suggest using the approach.
"Before we abandon the existing technique with its excellent local control and cosmetic long-term outcomes, we need much more long-term data," Norton said. As well, he said, "intraoperative radiotherapy requires expensive machinery and space and also ties up space that could otherwise be used for surgery."
Dr. Beryl McCormick, also of Memorial Sloan-Kettering, noted that a recent consensus statement from the American Society of Radiation Oncology recommends partial breast radiation only for women 60 or older with favorable early stage disease.
She said a study similar to the TARGIT trial, conducted at Memorial Sloan-Kettering, had good results but needed special equipment, such as an operating room shielded for high dose radiation, which would make it not applicable for most patients in the U.S.
That said, McCormick said she'd only recommend the procedure in the context of a clinical trial.
"The TARGIT trial is hypothesis generating, because of the unusually low dose given, but I wouldn't call it 'practice changing'," she said in an email.