From July 1999 to December 2003, 590 breast cancer patients (mean age, 59 years; range, 33–80 years) received ELIOT after breast-conserving surgery as sole radiation treatment modality (574 patients) or as an anticipated boost followed by external radiotherapy (16 patients). All patients had unicentric primary carcinoma, less than 2.5 cm in the largest diameter. Other 111 patients received ELIOT to the nipple-areola complex after subcutaneous mastectomy for extensive DCIS or minimally invasive carcinomas.

Nine of 16 patients treated with ELIOT combined with external radiotherapy received a 10 Gy boost by ELIOT followed by 44 Gy with external radiotherapy, while 7 received a 15 Gy boost by ELIOT followed by 40 Gy with external radiotherapy. One patient was treated using ELIOT at 21 Gy dose, followed by postoperative irradiation to the internal mammary chain (46 Gy), as an internal mammary node excised with radioguided surgery had proven positive.²

As regards patients treated with exclusive ELIOT after breast-conserving surgery, before reaching the full dose of 21 Gy we treated 9 patients with 17 Gy ELIOT and 6 with 19 Gy as part of the initial dose-finding study. The remaining 559 patients received 21 Gy prescribed at the 90% isodose as sole radiation treatment: all these patients were over 48 years, due to the inclusion criteria we established for our protocol. All patients were fully informed of the experimental nature of the treatment and signed an informed consent. A description of our ELIOT cases in the time interval described is given in Tables 1 and 2.

Most patients (479) received wide excision or quadrantectomy with sentinel node biopsy; 394 (82.3%) had a negative sentinel node: in these patients, axillary dissection was not performed. Sixty-six patients (13.7%) with sentinel node metastasis received complete axillary dissection; 19 (4%) patients with positive micrometastatic lymph nodes did not undergo axillary dissection; 100 patients received wide excision or quadrantectomy with complete axillary dissection due to the clinical suspicion of axillary metastases: 68 (68%) of them had positive axillary nodes at final histology, and 11 patients received simple quadrantectomy.

Finally, another 111 cases were submitted to ELIOT (16 Gy) to the nipple-areola complex during nipple-sparing subcutaneous mastectomy for multicentric in situ ductal carcinoma or for multicentric minimal breast carcinomas. These patients will be discussed in a separate report.

The ELIOT technique has already been described.^3–7 Briefly, 2 dedicated, mobile linear accelerators (Fig. 1) were used to deliver ELIOT: a Novac7 (Hitesys Srl, Latina, Italy) and, more recently, a Liac (Info&Tech, Roma, Italy), installed in 2 different operating rooms and delivering electron beams at high dose rate. The 2 linear accelerators, which can be easily maneuverd by means of motors acting on the wheels and the articulated arm, deliver electrons at the following different nominal energies: 3-5-7-9 (Novac7) and 4-6-8-10 MeV (Liac). Beam collimation is achieved by a hard-docking system, consisting of perspex round applicators, 5 mm thick. Flat-ended and bevelled (15° up to 45°) applicators of diameter ranging from 3 to 12 cm are available. The nominal source to surface distance is 80 to 100 cm for Novac7 and 60 cm for Liac. For radiation protection, a primary beam stopper, consisting of a trolley-mounted 1.5 cm thick lead shield, and some mobile 1.5 cm thick lead shieldings (100 cm long, 150 cm high) are provided.

Within the comprehensive Quality Assurance program for those dedicated linear accelerators, an in vivo dosimetry procedure, aiming at the check of the dose delivered to the patient, has been implemented.⁷

Side effects were evaluated according to the RTOG/EORTC Late Radiation Morbidity Scoring Scheme. Every patient was evaluated 1, 3, 6, and 12 months after surgery, and thereafter every 6 months, to look for early, intermediate and late complications. At follow-up, the area treated by ELIOT was identified by x-ray radiograms, on the basis of the radio-opaque markers left during surgery. The follow-up ranges from 4 to 57 months (mean, 24 months). No patients were lost to follow-up.

The present paper will deal with results of the 590 cases after breast-conserving surgery. The patients submitted to ELIOT to the nipple-areola complex during nipple-sparing mastectomy will be the subject of a separate report.

We noticed that lyponecrosis involved patients with higher portion of fat tissue in the breast; the age range was 46 to 80 years (mean age, 70.2 years): 3 patients were younger than 60 years, 1 was 66 years old, and 11 were older than 70 years. This complication appears to be more frequent in older patients with higher proportion of fat tissue in the breast, but the relatively low incidence of the event could not give us further evidence of other risk factors.

Three patients developed a new ipsilateral carcinoma in other quadrants of the breast 9, 14, and 17 months after ELIOT. In all 3 patients, the new primary carcinoma appeared clearly outside the radiation field, distant from theELIOT treatment. Five patients developed contralateral breast carcinoma. One of them developed a contralateral breast carcinoma 24 months after ELIOT (21 Gy); an ipsilateral breast carcinoma was also discovered at the time of the hospitalization for surgery. She was treated with bilateral wide excision and 21 Gy ELIOT to the contralateral breast at the time of second surgery. Three patients developed other primary tumors: one follicular non-Hodgkin lymphoma, one laryngeal carcinoma, and one medullary thyroid carcinoma. Thirteen patients (2.2%) developed distant metastases (Table 4): all of them had no sign of local relapse.

Breast-conserving surgery followed by radiotherapy is the standard treatment option for most women with clinical stage I/II invasive breast cancer.^8,9 Also, sentinel node biopsy has been confirmed as a safe and reliable technique to predict axillary status in most patients candidate to conservative surgery; this technique makes it possible to conserve the axillary lymph nodes in many breast cancer patients as well.^10–21 These 2 techniques combined constitute a minimally mutilating approach to breast cancer that achieves an acceptable local control and no difference in survival compared with mastectomy and axillary dissection.

In the field of radiation therapy for breast cancer, a question that has been recently revised is whether the entire breast needs to be irradiated following conservative surgery, or whether it is sufficient to treat a more limited volume of tissue surrounding the tumor bed, considering the recent data showing that 85% local recurrences develop in the scar area.¹ Moreover, in the same trial, in the group of patients older than 55 years, the incidence of local relapse was not influenced in the same significant way by radiotherapy as in the younger patients' group. The impact of radiotherapy on the local control of disease decreases with the increase of patients' age; the incidence of local relapse appeared to be the same in the radiotherapy and no-radiotherapy group in patients older that 65 years.

If a single session treatment could produce the same outcome as the conventional 6-week course of whole breast irradiation, this would substantially ease the difficulties of those women who have to contend with long waiting lists for radiotherapy or live a long way from a radiotherapy center. Equally important is the fact that this logistically simpler and quicker treatment will cost much less than conventional radiotherapy for breast cancer patients.

ELIOT is a promising feature in breast conservation: the reduction of the radiation field makes the exposure of normal tissues dramatically lower (Fig. 2), and the shortening of the radiation course from 5 to 6 weeks to one session is extremely positive in terms of patients' quality of life and costs. The reduction of the radiation field results in the so-called “partial breast irradiation,” that is, a topic under active investigation at the current time. Some interesting experiences have been published, with the aim of testing theimpact of partial breast irradiation on breast cancer treatment: different radiotherapy techniques were used for these studies.^22–29

We began clinical research on ELIOT in 1999. Our first task was to estimate the single dose of electrons biologically comparable to standard fractionated radiotherapy for breast cancer. To do this, we used the linear-quadratic surviving fraction model, otherwise known as multitarget surviving fraction model, which indicated that a single dose in the range 20 to 22 Gy is equivalent to 60 Gy delivered in 2 Gy daily fractions, 5 days a week over 6 weeks (ie, the dose required to control microscopic residual disease after breast resection).

We decided to err on the side of caution initially and began with intraoperative doses lower than this level and then increased them. We studied dose levels of 10-15-17-19 and 21 Gy: at the 2 initial dose levels, ELIOT was followed, as already mentioned, by a reduced course of external fractionated radiotherapy.^4,5,30,31

The toxicity of ELIOT is low; we had just 1 case of severe fibrosis that resolved spontaneously within one year from its observation. The other 18 cases (3%) of mild fibrosis did not cause cosmetic impairment. The 2 cases of skin retraction could be related to ELIOT, but also to a poor surgical result.

The 15 cases of lyponecrosis represent an issue we want to clarify with further follow-up: this nonsevere complication seems unrelated to postoperative infection and regarded mainly patients older than 70 years (11 of 15) with breast tissue entirely represented by fat.

The ELIOT technique with its limited field of electrons and the direct vision of the radiation field by the operators gives a guarantee against unnecessary irradiation of normal tissues. It is important to point out that the irradiation of the lung and the heart is completely avoided by the use of ELIOT.

A possible contraindication to the use of ELIOT was considered the clinical involvement of axillary lymph nodes.³² We think that there are no logical reasons for this position, as primary carcinoma, even if axillary involvement is present, may be of very limited dimension and therefore may be resolved with conserving surgery and local radiotherapy.

Patients' quality of life is influenced by the use of ELIOT: the daily stress that may be cause of depression during the long external radiotherapy course is solved with ELIOT. Indeed, patients usually do not even realize that they underwent radiotherapy during surgery.

The rate of breast cancer-related events observed up to now seem encouraging: the follow-up is ongoing, and the cumulative curve of intrabreast tumor reappearance appears very low. An advantage of ELIOT is that the delay in administering radiotherapy in cases given adjuvant anthracyclines can be avoided; there is evidence that the delay increases the risk of local recurrences.³³

One area of concern in the use of ELIOT is the management of positive surgical margins as positivity is discovered at final histology, a few days after surgery and intraoperative radiotherapy. The adoption of an extensive breast resection as a standard procedure in breast-conserving surgery keeps the incidence of positive surgical margins to very low rates. Moreover, data from our randomized Milan II trial showed that margin positivity did not influence the rate of local recurrences if effective radiotherapy is delivered.³⁴

Our results on ELIOT tolerance confirmed the positive impact of ELIOT on patients' quality of life: ELIOT is feasible and safe, and we are waiting for the long-term results on local control to definitively adopt the technique in the daily practice.