The results of two new studies published in TheLancet and LancetOncol suggest that targeted radiation therapy administered during surgery is a viable treatment option for women with early-stage breast cancer treated with partial mastectomy compared to the current conventional procedure, which requires postoperative radiation therapy for several weeks.
For the vast majority of women who undergo partial mastectomy (focal resection), they also receive a series of radiation treatments to the affected breast (called external beam radiation therapy (EBRT)). This can be very problematic for women who live far from a radiation center (especially if they live in remote or very remote areas).
In some cases, a percentage of patients who could have undergone partial mastectomy had to change their procedure to mastectomy, for the reasons mentioned above – such as not being able to continue radiation therapy after a partial mastectomy.
In the absence of radiation therapy, women who have undergone partial mastectomy are at risk for tumor recurrence, either at the site of the primary tumor or in the vicinity of the primary tumor. Several research groups have conducted studies to address these issues – mainly on how to administer radiation therapy to reduce the risk of recurrence, such as whether to administer a single dose of radiation therapy, whether to target radiation therapy to the primary tumor site, and whether to administer radiation therapy intraoperatively or postoperatively. Two recent studies published in TheLancent and LancetOncol reveal the efficacy of two different targeted therapies for these patients.
The TARGIT-A study
In TheLancet, an international team of scholars led by Prof. Michael Baum and Prof. Jayant Vaidya (from the University of London, UK) conducted the TARGIT study, which compares the effects of using standard EBRT treatment and TARGIT (radiotherapy to the tumor site using a miniature X-ray emission device), two different treatment modalities on tumor recurrence with a once-daily regimen of 3 to 6 weeks.
Over a period of more than 12 years, 1721 women were treated with TARGIT (treatment group) and 1730 women with standard EBRT (control group). Professors JayantVaidya and JeffreyTobias have been testing and evaluating the above mentioned treatment techniques in 33 different centers.
A total of 3451 patients were included in the final analysis in 2 separate groups of subjects. The first included 2298 patients, 1140 of whom received TARGIT in conjunction with their first surgery (as originally envisaged by the investigators) and a further 1158 patients who received standard EBRT, and the investigators compared these two different study approaches.
However, after requests from some clinicians, they expanded the study to include 1,143 new patients, 562 of whom were included in the EBRT group and another 581 in the TARGIT group, this time with a treatment regimen of TARGIT at 37 days after surgery.
The study was designed to be as responsive as possible to realistic treatment protocols, as female patients who had received TARGIT at the time of surgery were also treated again with EBRT after later demonstrating high-risk factors for recurrence. Overall, about 80 percent of patients in the TARGIT group completed their surgery and radiation treatment under one anesthetic without additional EBRT treatment.
The investigators noted that if the difference in 5-year local recurrence rates from these two different treatment regimens was less than 2.5%, then TARGIT treatment should be considered as effective as (not inferior to) standard treatment. In all subjects, the 5-year risk of local recurrence of breast tumors from these two different treatment regimens was less than the initially set 2.5%, implying that single TARGIT treatment was not inferior to EBRT treatment in terms of tumor control.
In addition, the overall mortality rate was 3.9% in the TARGIT group compared to 5.3% in the EBRT group, mainly due to lower mortality from cardiovascular death and other tumors associated with TARGIT treatment compared to EBRT treatment. When TARGIT was given in conjunction with partial mastectomy – as the investigators initially expected – local recurrence and mortality rates were similar in the TARGIT and EBRT groups, but mortality due to other causes was lower in the TARGIT group. (TARGIT/EBRT: 1.3%/4.4%), which led to the above results.
Professor Vaidya pointed out that the most important benefit of TARGIT for women with breast cancer is that patients can have all the local treatments they need at the same time as surgery, and that this approach causes fewer toxic effects on the breast, heart and other organs. Our findings therefore support the use of TARGIT in conjunction with local mastectomy in carefully screened patients, a treatment option that provides an additional option for patients and physicians to help develop individualized treatment plans, save time, money, and save the breast and even the patient’s life.
ELIOT Study
In LancetOncol, researchers from Italy, led by Professor Umberto Veronesi (European Oncology Institute, Milan), reported the results of their study, which focuses on a new approach to targeted radiotherapy (slightly different from that used previously) in which the investigators use radiation that releases electrons to target the primary site of the tumor ( electron intraoperative radiotherapy or ELIOT).
At the European Oncology Research Institute in Milan, 651 women were treated with ELIOT during partial mastectomy, while 654 women in the control group were treated with standard EBRT after partial mastectomy.
The investigators investigated true local recurrent lesions in the breast (occurring at the same site as the primary tumor), and recurrences that occurred in the ipsilateral operated breast. They found that after 5 years, the recurrence rate was significantly higher in the ELIOT group compared to the control group, with 21 (2.5%) women in the ELIOT group experiencing local recurrence and 35 (4.4%) women in the ELIOT group, compared to 4 (0.4%) women in the control group, if ipsilateral recurrence was included in the evaluation.
Although there was a difference in the recurrence rate, considering the overall survival rate, there was no significant difference in overall survival between the ELIOT group and the control group – 34 deaths in the ELIOT group compared to 31 deaths in the control group; therefore, there was no significant difference in mortality between the two groups. There were no significant differences between the two groups.
In patients in the ELIOT group, the investigators investigated the characteristics of recurrent tumors, which helped them identify several features associated with recurrence: including large tumors (>2 cm), and estrogen receptor negativity (ER negativity).
Professor Veronesi noted that for women treated with intraoperative radiotherapy, identifying the factors most likely to cause breast cancer recurrence can help us determine which patients are likely to benefit from subsequent external radiotherapy. Although our results show a significantly higher 5-year local tumor recurrence rate in women treated with ELIOT, we need to recognize that for some women, the benefit of not completing complete radiation therapy may outweigh the risk of increased risk of local recurrence.
Another encouraging result is that overall mortality after 5 years was not significantly different between the ELIOT and standard treatment groups. Intraoperative radiotherapy may help to further improve patients’ quality of life, and the results of our study could facilitate clinicians to better apply molecular biological factors in addition to conventional treatment and histological factors to identify those patients most suitable for partial breast radiotherapy.