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Archived Comments for: Electrons for intraoperative radiotherapy in selected breast-cancer patients: late results of the Montpellier phase II trial

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  1. In reply to: Lemanski C et al.

    stefano dall'oglio, Radiation Oncology Department, University Hospital, Verona, Italy

    9 October 2013

    In reply to: Lemanski C et al. Electrons for intraoperative radiotherapy in selected breast - cancer patients: late results of the Montpellier phase II trial. Radiation Oncology 2013, 8:191.

    The high local recurrence of 9.5% reported by Lemanski and colleagues in "Electrons for intraoperative radiotherapy in selected breast - cancer patients: late results of the Montpellier phase II trial" is inconsistent with our experience and that of other authors, for low risk women treated with just a single 21 Gy dose of electrons during breast conserving surgery (BCS). Even allowing that one of the recurrences represents a new cancer as stated by the authors, the recurrence rate would still be a very high 7.1%.

    We reported on 226 women treated with 21 Gy of electrons to the 80% depth, and had only one recurrence with a mean follow - up of 46 months (1). We updated our results at the San Antonio Breast Cancer Symposium in 2012 (2). We had 4 recurrences (1.8%) with a mean follow - up of 51 months; if we exclude the one triple negative patient that was given intraoperative electron radiotherapy (IOERT) because she was 75 years old, the recurrence rate now at 5 years median follow - up is only 1.3%. Our recurrence rates are similar to the 1.5% recurrence rate reported at 5 years by Leonardi for ASTRO guidelines - suitable accelerated partial breast irradiation (APBI) (3) and the 1.8% recurrence rate reported for ESTRO - guidelines suitable APBI (4); both studies are from the 1822 out - trial patients treated at the European Institute of Oncoogy (EIO, Milan, Italy), with a single dose of 21 Gy to the 90% isodose line. The ELIOT trial randomized data for ASTRO suitable women has also been reported at the latest ESTRO meeting to be 1.5% with a median follow -up of 5.7 years (5).

    What is concerning with the Lemanski study is that the recurrence rate is not better than similar low - risk patients treated with lumpectomy and no radiation at all. In a randomized trial for T1N0 women over 70 years who were also ER+ , patients were randomized to receive either Tamoxifen alone or additional whole breast irradiation (WBI) (6,7). The local recurrence at 5 and 10 years in the Tamoxifen only group was 4% and 9% respectively, compared to 1% and 2% for the irradiated patients. In another randomized study involving 869 women with predominantly T1G1-2, node negative and ER+ disease (similar to the Lemanski cohort), the 5 year local recurrence was 6.1% for those receiving Tamoxifen only versus 2.1% for those also receiving radiation (8).

    One can only conclude that the radiation technique used by Lemanski was probably inadequate since it did not properly treat the volume at risk. It appears that Lemanski used his pioneering IOERT boost technique (9) which produced excellent long - term oncologic and cosmetic results, and merely increased the IOERT dose to 21 Gy without consideration of the volume irradiated. With boost, the tissue underlying the re - approximated excision cavity receives adequate irradiation from the post - operative WBI. Thus, selecting an energy to treat to the 90% isodose line at a 1.5 to 2 cm depth below the excision cavity is appropriate. In the current study, Lemanski apparently estimated the thickness of the breast tissue to be treated, and then used 6 or 9 MeV energies, which would give a 90% depth between 1.7 cm and 2.8 cm. However, this depth is very unlikely to adequately irradiated the deep - seated tissues down to the chest wall (CW). With single - fraction breast IOERT, it is critical to treat to the CW to achieve local control. Guenzi (10) demonstrated that treating to the CW with single fraction irradiates a volume similar to that used in 3D conformal APBI studies.

    It is also not clear if the 4 cm applicator size that Lemanski used was adequate. Lemanski provides no breakdown of tumor size versus applicator size for recurrences. Adequate appplicator size is also critical in the technique as tissues just inside the walls of the applicators have a cold spot in the first 5 mm and these tissues do not receive the full prescribed radiation dose. In the ELIOT trial and the Leonardi publications, the field size used was 4 cm. Leonardi (5) indicates that too small a field size could be a factor in recurrences in singe - dose IOERT treatment. The new standard at the EIO for ELIOT is now 6 cm, with an occasional use of 5 cm for very small lesions (Orecchia R, personal communication). In our series, only 5% of the patients had a field size as small as 4 cm.

    Adequate volume irradiation with dose uniformity is critical for the success of any APBI approach, particularly single - fraction treatments. It appears that the Lemanski study may not have taken the irradiated volume into account.

    Stefano Dall'Oglio, MD
    Department of Radiation Oncology,
    University Hospital, Verona, Italy

    References

    1. Maluta S, Dall'Oglio S, Marciai N, et al. Accelerated partial breast irradiation using only intraoperative electron radiation therapy in early stage breast cancer. Int J Radiat Oncol Biol Phys 84, 145 - 152, 2012.
    2. Dall'Oglio S, Maluta S, Marciai N, et al. Intraoperative electron radiotherapy in early - stage breast cancer: a mono - institutional experience. Poster presentation, Abstr P3-13-07. San Antonio Breast Cancer Symposium, 2012.
    3. Leonardi MC, Maisonneuve P, Mastropasqua MG, et al. How do the ASTRO consensus statement guidelines for the application of accelerated partial breast irradiation fit intraoperative radiotherapy? A retrospective analysis of patients treated at the European Institute of Oncology. Int J Radiat Oncol Biol Phys 83, 806 - 813, 2012.
    4. Leonardi MC, Maisonneuve P, Mastropasqua MG, et al. Accelerated partial breast irradiation with intraoperative electrons: using GEC - ESTRO recommendations as guidance for patient selection. Radiother Oncol 106, 21 - 27, 2013.
    5. Orecchia R. Intraoperative partial breast irradiation: the ELIOT trial results at 5 years. Abstr OC-0234. Presented at the 2nd ESTRO forum, Geneva 2013.
    6. Hughes KS, Schnaper LA, Berry D, et al. Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med 351, 971 - 977, 2004.
    7. Hughes KS, Schnaper LA, Bellon JR, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long - term follow - up of CALGB 9343. J Clin Oncol 31, 2382 - 2387, 2013.
    8. Potter R, Gnant M, Kwasny W, et al. Lumpectomy plus tamoxifen or anastrozole with or without whole breast irradiation in women with favorable early breast cancer. Int J Radiat Oncol Biol Phys 68, 334 - 340, 2007.
    9. Lemanski C, Azria D, Thezenas S, et al. Intraoperative radiotherapy given as a boost for early breast cancer: long - term clinical and cosmetic results. Int J Radiat Oncol Biol Phys 64, 1410 - 1415, 2006.
    10. Guenzi M, Fozza A, Blandino G, et al. Focus on the actual clinical target volume irradiated with intraoperative radiotherapy for breast cancer. Anticancer Research 32, 4945 - 4950, 2012.

    Competing interests

    None.

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