Clinical Investigation
Intraoperative Radiotherapy in Early-Stage Breast Cancer: Results of the Montpellier Phase II Trial

Presented in part at the International Society of Intraoperative Radiation Therapy, Madrid, Spain June 10–13, 2008, and at the 50th annual meeting of the American Society for Therapeutic Radiation Oncology, Boston, MA, Sept 21–25, 2008.
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Purpose

We recently presented the intraoperative radiotherapy (IORT) technique given as a reliable alternative to conventional boost radiation after breast-conserving surgery. The low crude numbers of recurrence in elderly patients led us to investigate the feasibility and the efficacy of this procedure as a sole treatment.

Methods and Materials

We included 94 patients older than 65 years in this phase II trial. Among them, 42 patients presented with all the inclusion criteria, i.e., stages pT0 to pT1 and pN0, ductal invasive unifocal carcinoma, and tumor-free margin of >2 mm. IORT was delivered using a dedicated linear accelerator. One 21-Gy fraction was prescribed and specified at the 90% isodose, using electrons. In vivo dosimetry was performed for all patients. The primary endpoint was the quality index. Secondary endpoints were quality of life, local recurrences, cosmetic results, and specific and overall rates of survival.

Results

The median follow-up was 30 months (range, 12–49 months), and median age was 72 years (range, 66–80 years). The median tumor diameter was 10 mm. All patients received the total prescribed dose. No acute grade 3 toxicities were observed. Endpoints for all but one patient corresponded to acceptable quality index criteria. Pretreatment quality-of-life scores were maximal, and no significant decrease was observed during follow-up. Cosmesis was good to excellent at 6 months. Two patients experienced recurrence but underwent salvage mastectomy.

Conclusion

Our results confirm that exclusive partial-breast IORT is feasible for treating early-stage breast cancer in the elderly. IORT may be considered an alternative treatment for a selected population and offers a safe one-step treatment.

Introduction

Several randomized trials have established the equivalence of breast-conserving therapy (BCT) to mastectomy in terms of overall survival 1, 2, 3. BCT, i.e., breast-conserving surgery followed by a course of postoperative radiotherapy (RT), is now considered the current standard of care for patients with early-stage breast cancer (4). Routine whole-breast RT (WBRT) comprises 50 Gy in daily fractions for 5 weeks (4). The additional application of an external boost of 10 to 16 Gy to the tumor bed leads to excellent local tumor control, with local recurrence rates around 6% after a median of 10 years follow-up (5). However, considering the low and focal local recurrence rates, the concept of accelerated partial breast irradiation (PBI) therapy has gained widespread interest employing various methods. Intraoperative RT (IORT) is one method that may offer the advantage of an excellent delineation of the tumor bed under visual control, very good dose homogeneity, and high sparing of normal tissue 6, 7.

Given as a boost after breast-conserving surgery, IORT is now considered the reliable alternative to a conventional postoperative fractionated boost radiation (8). We recently showed that this technique is efficiently able to prevent local recurrence and allows excellent cosmetic results, with a median follow-up of 9 years (9). In 2004, we started a strict program to investigate the feasibility of IORT as the sole treatment in very-low-risk patients, namely those older than 65 years, suffering from T1N0M0 (10) invasive ductal carcinoma. We report here the results of this monocentric phase II trial (RADELEC) with a median follow-up of 30 months.

Section snippets

Patient selection criteria

Between November 2004 and November 2007, 96 women were included in this phase II trial evaluating IORT delivered to the tumor bed as the exclusive adjuvant RT. Inclusion criteria were T1N0M0 invasive unifocal ductal carcinoma (10) and an age of ≥65 years. All patients underwent staging tests including chest x-ray, bone scan, and liver ultrasonography to rule out metastatic disease at diagnosis. Local evaluation consisted of mammography and breast ultrasonography (magnetic resonance imaging was

Patient, tumor, and treatment details

Ninety-four patients agreed to participate in this trial and signed the informed consent before surgery. Of these, 42 patients were actually included according to the study criteria. The main reasons for nondelivery of IORT were (i) pT/pN restaging during the IORT pathology assessment (n = 29 patients), (ii) operative room availability (n = 6 patients), (iii) machine disorder (n = 3 patients), (iv) anesthesia complications (n = 2 patients), and informed consent withdrawal (n = 1 patient). In

Discussion

The updated publication of the collaborative meta-analyses based on individual patient data confirmed the positive impact of adjuvant WBRT in terms of locoregional recurrence with a long-term follow-up (4). These results confirm that the greater the reduction in local events obtained during the first 5 years, the greater the specific survival will be over the next decade. In addition, WBRT routinely associated with a 16-Gy boost is able to produce similar proportional reductions in local

Conclusions

In conclusion, and from the results of this phase II study, we are continuing with a prospective database, evaluating the carcinogenic and long-term side effects of a single 21-Gy IORT fraction on patients older than 65 years, presenting with a HR-positive tumor (<2 cm) with a negative sentinel node. We suggest that this selected population, at very-low risk of local recurrence, is an excellent group in which to administer a one-shot procedure, avoiding a 5- to 6-week postoperative treatment.

Acknowledgments

The authors thank Frances Godson for excellent editorial assistance.

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    Claire Lemanski and David Azria contributed equally to this work and should be considered as joint first authors.

    Conflict of interest: none.

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