Conference Update

ASTRO 2015: Partial as good as whole breast irradiation in early breast cancer

Oncology
5 years ago, OP Editor

For the first time with clear and positive evidence, women with early breast cancer treated with accelerated partial-breast irradiation (APBI) did equally well compared with those who received standard whole breast irradiation (WBI), with no difference in rate of local recurrence, disease free survival and 5-year overall survival demonstrated in recent randomized control trial (RCT).1,2

Adjuvant radiation therapy using WBI after breast-conserving surgery is widely accepted as standard treatment of early stage breast cancer over the past 30 years. However, up to 50% patients who were clinically qualified for breast conservation underwent mastectomy, according to an analysis of US SEER 18 database.3 One of the most important reasons for that was the length of adjuvant WBI.

The APBI technique involves radiotherapy for a much shorter period, i.e., 2-5 days and compared with 3-7 weeks with WBI, and results in reduced radiation exposure to the breast and its surrounding area, particularly the heart. There are several types of ABPI, but the results from previously trials that used an intraoperative radiotherapy device (including the TARGIT and ELLIOT trials) have been negative, i.e., with more local recurrence.

The current trial, presented at the late-breaking session of the 57th annual meeting of American Society for Radiation Oncology (ASTRO)1 and simultaneously published in the Lancet on 19th October in 2015, carefully delivered the radiation directly to the tumor bed using muticatheter brachytherapy based ABPI. The implantation of small radioactive seeds was CT-guided and under light anesthesia, explained by the lead author Dr. Vratislav Strnad, MD, professor of radiation oncology at the University Hospital Erlangen in Germany. Since catheter was often inserted through scar tissue, no noticeable marks were left on the skin after the therapy.

A total of 1184 women with low-risk invasive and ductal carcinoma in situ treated with breast-conserving surgery were recruited in this European trial. The patients were randomized to receive either WBI (total dose, 50-50.4 GY, delivered in 25 to 28 fractions) or muticatheter brachytherapy-based ABPI described above (either 32 Gy in eight fractions or 30.3 Gy in seven fractions). The primary endpoint was local recurrence. Median follow-up duration was 6.6 years.

Dr. Strnad reported no differences were seen in terms of local recurrence (primary endpoint), disease-free survival and overall survivals between two groups in 5-year observation period. As the absolute change of local recurrence was less than +3% under ABPI arm (pre-defined), ABPI is considered non-relevant non-inferior to WBI. Statistical assessment by relating the 95%CI of the difference confirmed the results.

 

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No grade 4 late side-effects were reported. The 5-year risk of grade 2–3 late side-effects to the skin was 3.2% with APBI versus 5.7% with whole-breast irradiation (p=0·08), and 5-year risk of grade 2–3 subcutaneous tissue late side-effects was 7.6% versus 6.3% (p=0.53). The risk of severe (grade 3) fibrosis at 5 years was 0.2% with whole-breast irradiation and 0% with APBI (p=0.46).

“The results of our phase 3 study show that, at present, multicatheter brachytherapy is an effective and viable APBI treatment option for low-risk breast cancer patients after breast-conserving surgery,” Dr Strnad concluded.2

Can APBI become a new standard based on the current non-inferiority trial?

“We think not”, written in the Lancet 4 by Dr. Charlotte Coles, MD, the consultant clinical oncologist at Addenbrookes Hospital from Cambridge in United Kingdom, and John R. Yarnold, MD, the consultant clinical oncologist in Academic Radiotherapy Unit at the Royal Marsden Hospital in London .Although this trial presents maturing data, but further evidence is required from the ongoing or unreported trials with ABPI, which involved about 14,000 patients in total.

Furthermore, the possible benefits of APBI, such as short overall treatment time and decreased heart dose, are now reflected with modern WBI. A 10-year study comparing 3-week with 5-week WBI demonstrated that shorter treatment time reduced side-effects without compromising local control. The recent advance in WBI with cardiac sparing technique has also substantially reduced heart dose.

“We know that breast cancer represents a spectrum of different diseases, with variations in prognosis, and that radiotherapy, is no longer a one-size-fits-all strategy, which ranges from highly complex treatments to the breast and regional lymph nodes, to complete avoidance of any radiation”.

“It is likely that APBI will have a place within this array of treatment”. However, the challenge will be to select more appropriate treatment and to personalize the therapy based on tumor biology.

 

  1. Strnad V, et al., Accelerated Partial Breast Irradiation Using Sole Interstitial Multicatheter Brachytherapy vs Whole Breast Irradiation for Early Breast Cancer: 5-year Results of a Randomized Phase III Trial – Part I: Local Control and Survival Results. (LBA7). American Society for Radiation Oncology (ASTRO) 57th Annual Meeting, 18-21 October 2015, San Antonio, USA
  2. Strnad V, Ott OJ, Hildebrandt G, et al., 5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial. Lancet 2015 epub 19-October-2015.
  3. Showalter, SL, Grover, S, Sharma, S, Lin, L, and Czerniecki, BJ. Factors influencing surgical and adjuvant therapy in stage I breast cancer: a SEER 18 database analysis. Ann Surg Oncol. 2013; 20: 1287–1294.
  4. Coles CE and Yarnold JR. Accelerated partial breast irradiation: the new standard? Lancet 2015 epub 19-October-2015.

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