The technique radioactive seed localization has been shown to work just as effectively as the long-established standard, wire-guided localization among women with nonpalpable invasive breast cancer or ductal carcinoma in situ (DCIS). The two techniques were compared in a Danish multicenter randomized controlled clinical trial and results were presented at the 2016 San Antonio Breast Cancer Symposium (Abstract S3-08).
“The standard of localization has been wire-guided localization for many years; however, this method is believed to entail a relatively high number of positive resection margins,” said Linnea Langhans, MD, the study's lead researcher from Rigshospitalet & Herlev Hospital, University of Copenhagen, Denmark. Positive resection margins indicate the presence of tumor cells after lesion excision. “Furthermore, the increasing number of nonpalpable breast lesions causes a need for more flexible course of treatment than offered by the wire-guided procedure.”
The increasing number of nonpalpable lesions detected can be attributed to the rising use of breast cancer screening methods, such as mammography, ultrasonography, and MRI of the breast, among asymptomatic patients.
Wire-guided localization is performed when excisional biopsies or breast-conserving surgery is desired and involves inserting a wire into the breast lesion before surgery so that the surgeon can detect the lesion during surgery. Some of the limitations of this technique include the requirement of performing localization on the same day as surgery, displacement of the wire before surgery, and patient discomfort.
“Alternative methods, especially in the field of radioguided surgery, have been developed trying to overcome these difficulties,” Langhans said. “One of these methods is radioactive seed localization.”
Radioactive seed localization involves using imaging guidance to place a small titanium seed containing iodine 125 into the lesion and using a handheld gamma probe during surgery to find the seed and, in turn, the lesion.
“The aim of this randomized controlled trial was to compare the rate of positive resection margins between radioactive seed localization and wire-guided localization after breast-conserving surgery,” Langhans said. Positive margins were defined as the presence of cancer cells less than 2 mm from the inked tissue, according to Danish guidelines.
Study researchers prospectively enrolled women with nonpalpable inflammatory breast cancer or DCIS that was found using ultrasonography. The participants had to be eligible for breast-conserving surgery. Eligible participants were then randomized to receive radioactive-seed localization or wire-guided localization.
“Patients' pain perception, duration of the surgical procedure and weight of the excised specimen were our secondary outcomes,” Langhans noted. “The main outcome was margin status at the final microscopic examination.”
Promptly after the seed or wire was placed, patients scored their pain related to the procedure, and the duration of the breast-conserving surgery was defined as time from skin incision to completed excision of the marked lesion. The surgical specimen was weighed during surgery.
The intention-to-treat population had 319 patients, of which 12 had to be excluded from analysis because the participants did not receive the assigned intervention.
The two groups of participants had similar baseline characteristics, and the only statistically significant difference found was the wire group had more patients with DCIS lesions that the seed group (P=0.006). This difference was not particularly concerning because the total number of DCIS patients was low. The invasive breast cancers were similar between the two groups.
“Radioactive seed localization and wire-guided localization provided similar positive margin rates in patients with nonpalpable breast lesion invasive breast cancer or DCIS, and we were not able to see a difference in the duration of the surgical procedure, weight of excised specimen or patient pain perception,” Langhans explained. Specifically, positive margins were found for 23 lesions from seed group and 26 lesions from the wire group.
These findings align with those of two previous randomized trials, a Canadian study from 2011 (Ann Surg Oncol 2011;18:3407-3414) and a U.S. study from 2016 (Breast J 2016;22(2):151-157).
“It was worth mentioning that the surgical procedures were performed by 17 different breast surgeons and the experience gained with the seed procedure was very limited compared to the wire procedure,” Langhans said. These 17 surgeons, who had little experience with the seeds before the study, performed 195 seeds but did not perform enough seeds to determine whether their performance of the technique had improved.
The seed localization technique has a “significant learning curve” noted Henry Cain, MD, FRCS, consultant oncoplastic breast surgeon at the Royal Victoria Infirmary, Newcastle upon Tyne, U.K., during the question-and-answer session.
If the learning curve is overcome by the surgeons, weight of excised specimen and duration of procedure could decrease.
During a new session at the symposium, View From the Trenches: What Will You Do Monday AM?, experts critiqued studies from the general session, and this Danish study was one of them. Monica Morrow, MD, FACS, surgical oncologist at Memorial Sloan Kettering Cancer Center, critiqued the choice of endpoint: margin status.
“If the guide is accurately positioned, there's not really a priori reason to believe that this should impact margin status,” Marrow said. “Margin status is impacted by the characteristics of the tumor, the experience of the surgeon, but it really shouldn't be impacted by the guide. This study showed that is wasn't.”
When asked to comment on Marrow's critique, Mark J. Dryden, MD, Associate Professor of Radiology in the Department of Diagnostic Radiology at the University of Texas MD Anderson Cancer Center, told Oncology Times, “I agree with Dr. Morrow that there are multiple variables that can affect margin status in patients undergoing attempt at breast-conserving therapy, such a tumor characteristics and surgeon experience, but I disagree that one can just infer that one method of localizing nonpalpable breast lesions is inherently as accurate and effective as another method.”
He went on to explain that when looking at surgical margin status outcome, localization method is a variable to consider in addition to tumor characteristics and surgeon experience. “To say that radioactive seed localization is just as effective as wire-guided localization, studies such as the Danish study as well as our own study at MD Anderson are needed for nonbiased confirmation.”
Radioactive seed localization offers surgeons and patients several advantages over the traditional wire placement method.
“The major advantages of radioactive seed localization is the flexibility of the procedure,” Langhans said. “The seed can be located in the breast tissue several days before surgery due to the long half-life of iodine 125 and the patient can be scheduled for surgery in the morning.”
Morrow added, “If you happen to like to localize lymph nodes that have clips in them after neoadjuvant therapy, it is infinitely more humane to do that by dropping a seed into that lymph node than trying to drop a wire into someone's axilla.”
Also, most patients are candidates for radioactive seed localization. Only rarely do patients have a lesion that is not suitable for this technique.
“In our experience at MD Anderson, the only lesions that we feel are not a good candidate for radioactive seed localization are heavily calcified masses, which is not a common presentation of breast lesions, especially breast cancers,” Dryden noted. “We had a case where a radioactive seed was implanted centrally into a heavily calcified mass, and when the surgical specimen was sent to pathology for sectioning, the seed was inadvertently transected, which led to other issues of dealing with the ‘escaped’ radioisotope.”
However, one disadvantage is the seeds are radioactive and therefore regulated by the state as radioactivity.
“In New York State, loss of one of these seeds is a reportable radiation incident to the state,” Morrow said. “Because they're fixed into the tissue with little fine hairs, they fall out very easily, [and] end up on the floor of the operating room or in the suction device, so you have to be aware of that.”
Overall though, Morrow supports the use of radioactive seed localization. She said that from a practical point of view, this technique is a “more convenient way” to localize nonpalpable breast cancer and is “nicer” for patients and surgeons.
Dryden agreed: “I think the data does show that there is enough evidence to safely implement radioactive seed localization as the standard of care in the pre-surgical localization of nonpalpable breast lesions. The main limitation of using radioactive seed localization in the U.S. is the numerous rules and regulations that must be adhered to when using radioisotopes in the surgical or medical setting. Those rules and regulations do not apply to other localization methods that do not use radioisotopes.”
“We believe that there is enough evidence to safely implement radioactive seed localization for nonpalpable invasive breast cancer given that all studies have reported similar positive margin rates when comparing the seed and the wire,” Langhans said. “In most of these studies, the number of patients with DCIS is limited and more evidence is probably needed for these patients.”
The results of this Danish study have been accepted for publication in Annals of Surgery.
Christina Bennett is a contributing writer.