Robotic Stereotactic Boost in Early Breast Cancer, a Phase 2 Trial.

PURPOSE: To evaluate the feasibility and toxicity of a single-fraction 8-Gy stereotactic boost after whole-breast irradiation in early breast cancer. The primary aim of this phase 2 study was to evaluate cutaneous breast toxicity using National Cancer Institute Common Terminology Criteria for Adverse Events (version 4) 3 months after the boost. Secondary objectives were local control, survival, and patient-reported quality of life using the European Organisation for Research and Treatment of Cancer QLQ-C30 and breast-specific European Organisation for Research and Treatment of Cancer QLQ-BR 23 questionnaires. METHODS AND MATERIALS: Patients with invasive ductal or lobular pT1-2 breast cancer treated with lumpectomy with clear margins and pN0 were included. Patients requiring chemotherapy were excluded. RESULTS: Twenty-eight eligible patients received the planned boost, and 26 had hormonal therapy. The procedure was technically successful without procedural complications. A median of 3 fiducials were tracked, and 115 beams were used. There were 22 acute grade 1 breast skin toxicities, including fibrosis, pain, erythema, or pigmentation. There were 2 acute grade 2 erythemas. Median skin boost dose was inversely correlated with acute skin toxicity (P = .028). QLQ-C30 scores revealed acute dyspnea and arm symptoms without correlation to the boost dose. Breast symptom QLQ-BR23 scores did not deteriorate, although upset with hair loss and systemic side effects of hormonal therapy were observed. After a median follow-up of 38 months, 1 patient had in-boost-field relapse, and there were 5 late grade 1 and 1 grade 2 skin toxicities. CONCLUSIONS: Single-fraction stereotactic boost after conventional whole-breast irradiation in early breast cancer is feasible with minor toxicities. Quality of life and specific breast items showed excellent patient acceptance.

Long-term results of hypofractionated radiotherapy and hormonal therapy without surgery for breast cancer in elderly patients.

BACKGROUND AND PURPOSE: To evaluate early and late reactions, local control, disease-free survival, cause-specific survival, and overall survival of elderly breast cancer patients treated with definitive once-a-week hypofractionated radiotherapy together with hormonal therapy. PATIENTS AND METHODS: Between 1987 and 1999, 115 patients with a median age of 83 presenting with 124 non-metastatic breast carcinoma were treated with definitive once weekly hypofractionated radiotherapy associated with hormonal therapy. The main reasons for adopting this schedule were patient refusal of surgery, very old age, locally advanced case, and/or comorbid disease. Radiation was delivered as once-a-week, 6.5 Gy for a total breast dose of 32.5 Gy in five fractions, followed with 1-3 fractions of 6.5 Gy to the tumour site. The median follow-up was 41 months. RESULTS: Neoadjuvant hormonal therapy led to 56% reduction of the tumour volume. Late reactions occurred in 46 patients; they were mild to moderate in 87% of these patients. The Kaplan-Meier rate was 52% of patients, with 6% experiencing grade 3 reactions. The 5-year local progression-free rate was 78%. The corresponding cause-specific survival was 71%, and was influenced by T classification, nodal status, oestrogen receptors and the total dose. The first three factors retained an independent prognostic impact on multivariate analysis. The 5-year overall survival was 38%. It was affected by the T classification, lymph node involvement and the performance status (PS). Using a multivariate analysis, only T classification and PS were identified as independent factors regarding overall survival. CONCLUSIONS: Definitive hypofractionated radiotherapy allows a good local control, with acceptable toxicity. This schedule associated with hormonal therapy is a good alternative to surgery in non-operable old patients and in case of patient refusal to surgery and to standard fractionation.

Long-term results of adjuvant hypofractionated radiotherapy for breast cancer in elderly patients.

PURPOSE: To evaluate early and late reactions, local control, disease-free survival, cause-specific survival, and overall survival of elderly breast cancer patients treated with adjuvant once-weekly hypofractionated radiotherapy (RT). METHODS AND MATERIALS: Between 1987 and 1999, 150 patients (median age, 78 years) who presented with 151 nonmetastatic breast tumors were treated with surgery and then adjuvant hypofractionated RT. The clinical stage distribution was as follows: T1 in 47.7%, T2 in 43.2%, T3 in 6.1%, and T4 in 3.0%. Axillary lymph nodes were positive in 33.8% of cases. Estrogen receptors were present in 89.9%, and progesterone receptors in 77.3%. Conservative breast surgery was performed in 71.5% and total mastectomy in 28.5%. RT was delivered once weekly in five fractions of 6.5 Gy to a total dose of 32.5 Gy. A boost was delivered to the tumor bed in 33.1%. Adjuvant hormonal therapy was given in 76.2% of patients. The median follow-up was 65 months. RESULTS: The Kaplan-Meier rate of all grades of early skin reactions was 26.5%, and the rate of all late reactions was 45.5%, mainly Grades 1 and 2. Early and late reactions were greater in those who underwent boost RT. The long-term local recurrence rate was 2.3%. The 5-year and 10-year disease-free survival rate was 80% and 71.5%, respectively. The corresponding rates for cause-specific survival were 89.1% and 77.6%. The 5-year and 10-year overall survival rate was 71.6% and 46.5%, respectively. These endpoints were influenced by tumor size, lymph node status, and hormone receptor status to varying degrees; however, tumor size appeared to be a major determinant on multivariate analysis. CONCLUSIONS: This hypofractionated RT scheme resulted in mild early reactions and acceptable late toxicity, in addition to providing excellent long-term local control. It can be proposed to patients who would have difficulties sustaining daily treatment because of old age or disabling associated disease.

Atlas-based automatic segmentation of MR images: validation study on the brainstem in radiotherapy context.

PURPOSE: Brain tumor radiotherapy requires the volume measurements and the localization of several individual brain structures. Any tool that can assist the physician to perform the delineation would then be of great help. Among segmentation methods, those that are atlas-based are appealing because they are able to segment several structures simultaneously, while preserving the anatomy topology. This study aims to evaluate such a method in a clinical context. METHODS AND MATERIALS: The brain atlas is made of two three-dimensional (3D) volumes: the first is an artificial 3D magnetic resonance imaging (MRI); the second consists of the segmented structures in this artificial MRI. The elastic registration of the artificial 3D MRI against a patient 3D MRI dataset yields an elastic transformation that can be applied to the labeled image. The elastic transformation is obtained by minimizing the sum of the square differences of the image intensities and derived from the optical flow principle. This automatic delineation (AD) enables the mapping of the segmented structures onto the patient MRI. Parameters of the AD have been optimized on a set of 20 patients. Results are obtained on a series of 6 patients' MRI. A comprehensive validation of the AD has been conducted on performance of atlas-based segmentation in a clinical context with volume, position, sensitivity, and specificity that are compared by a panel of seven experimented physicians for the brain tumor treatments. RESULTS: Expert interobserver volume variability ranged from 16.70 cm(3) to 41.26 cm(3). For patients, the ratio of minimal to maximal volume ranged from 48% to 70%. Median volume varied from 19.47 cm(3) to 27.66 cm(3) and volume of the brainstem calculated by AD varied from 17.75 cm(3) to 24.54 cm(3). Medians of experts ranged, respectively, for sensitivity and specificity, from 0.75 to 0.98 and from 0.85 to 0.99. Median of AD were, respectively, 0.77 and 0.97. Mean of experts ranged, respectively, from 0.78 to 0.97 and from 0.86 to 0.99. Mean of AD were, respectively, 0.76 and 0.97. CONCLUSIONS: Results demonstrate that the method is repeatable, provides a good trade-off between accuracy and robustness, and leads to reproducible segmentation and labeling. These results can be improved by enriching the atlas with the rough information of tumor or by using different laws of deformation for the different structures. Qualitative results also suggest that this method can be used for automatic segmentation of other organs such as neck, thorax, abdomen, pelvis, and limbs.

A networking for patient recruitment: the experience of choroidal melanoma.

The organization of a networking for patient recruitment is a main concern for a new facility using charged particles. The experience of choroidal melanoma in Nice demonstrates the possibility to create "de novo" a protontherapy center treating a sufficient number of patients. The influence of the opening of new facilities is analyzed.

Automatic three-dimensional model for protontherapy of the eye: preliminary results.

Recently, radiotherapy possibilities have been dramatically increased by software and hardware developments. Improvements in medical imaging devices have increased the importance of three-dimensional (3D) images as the complete examination of these data by a physician is not possible. Computer techniques are needed to present only the pertinent information for clinical applications. We describe a technique for an automatic 3D reconstruction of the eye and CT scan merging with fundus photographs (retinography). The final result is a "virtual eye" to guide ocular tumor protontherapy. First, we make specific software to automatically detect the position of the eyeball, the optical nerve, and the lens in the CT scan. We obtain a 3D eye reconstruction using this automatic method. Second, we describe the retinography and demonstrate the projection of this modality. Then we combine retinography with a reconstructed eye, using a CT scan to get a virtual eye. The result is a computer 3D scene rendering a virtual eye into a skull reconstruction. The virtual eye can be useful for the simulation, the planning, and the control of ocular tumor protontherapy. It can be adapted to treatment planning to automatically detect eye and organs at risk position. It should be highlighted that all the image processing is fully automatic to allow the reproduction of results, this is a useful property to conduct a consistent clinical validation. The automatic localization of the organ at risk in a CT scan or an MRI by automatic software could be of great interest for radiotherapy in the future for comparison of one patient at different times, the comparison of different treatments centers, the possibility of pooling results of different treatments centers, the automatic generation of doses-volumes histograms, the comparison between different treatment planning for the same patient and the comparison between different patients at the same time. It will also be less time consuming.

Accelerated partial breast irradiation in the elderly: 5-year results of high-dose rate multi-catheter brachytherapy.

OBJECTIVE: To evaluate clinical outcome after accelerated partial breast irradiation (APBI) in the elderly after high-dose-rate interstitial multi-catheter brachytherapy (HIBT). METHODS AND MATERIALS: Between 2005 and 2013, 70 patients underwent APBI using HIBT. Catheter implant was performed intra or post-operatively (referred patients) after lumpectomy and axillary sentinel lymph node dissection. Once the pathological results confirmed the indication of APBI, planification CT-scan was performed to deliver 34 Gy/10f/5d or 32 Gy/8f/4d. Dose-volume adaptation was manually achieved (graphical optimization). Dosimetric results and clinical outcome were retrospectively analyzed. Physician cosmetic evaluation was reported. RESULTS: With a median follow-up of 60.9 months [4.6 - 90.1], median age was 80.7 years [62 - 93.1]. Regarding APBI ASTRO criteria, 61.4%, 18.6% and 20% were classified as suitable, cautionary and non-suitable respectively. Axillary sentinel lymph node dissection was performed in 94.3%; 8 pts (11.5%) presented an axillary involvement. A median dose of 34 Gy [32 - 35] in 8 to 10 fractions was delivered. Median CTV was 75.2 cc [16.9 - 210], median D90 EQD2 was 43.3 Gy [35 - 72.6] and median DHI was 0.54 [0.19 - 0.74]. One patient experienced ipsilateral recurrence (5-year local free recurrence rate: 97.6%. Five-year specific and overall survival rates were 97.9% and 93.2% respectively. Thirty-four patients (48%) presented 47 late complications classified grade 1 (80.8%) and grade 2 (19.2%) with no grade ≥ 3. Cosmetic results were considered excellent/good for 67 pts (95.7%). CONCLUSION: APBI using HIBT and respecting strict rules of implantation and planification, represents a smart alternative between no post-operative irradiation and whole breast irradiation delivered over 6 consecutive weeks.

Local treatment options for ipsilateral breast tumour recurrence.

PURPOSE: In case of ipsilateral breast tumour recurrence (IBTR), radical mastectomy represents the treatment option frequently proposed. A second conservative treatment (2ndCT) has been proposed using either lumpectomy alone or associated with a re-irradiation of the tumor bed. However, in both clinical situations, the proof level of such therapeutic approaches remains low, based on cased-series or retrospective studies (level C). MATERIAL AND METHODS: In order to assess the different strategies of local treatment proposed in case of IBTR, a PubMed literature review was performed using the following keywords: breast cancer, ipsilateral recurrence, mastectomy, radiation therapy, brachytherapy. Four different salvage options were analyzed: (a) salvage mastectomy alone; (b) salvage mastectomy with postoperative re-irradiation; (c) 2ndCT with surgery alone; (d) 2ndCT with re-irradiation. RESULTS: The rate of second local recurrence is about 10% [3-32%], about 25% [7-36%] and about 10% [2-26%], after salvage mastectomy, salvage lumpectomy alone or combined with a re-irradiation of the tumor bed respectively. However, the 5-year overall survival rates after salvage mastectomy and 2ndCT seem to be equivalent (≈75%) mainly influenced by distant metastatic progression. CONCLUSION: In terms of Evidence Based Medicine, different options can be discussed such as Phase III or II randomized trials comparing salvage mastectomy versus 2ndCT, retrospective studies based on a matched-pair analysis or observatory studies. Those study designs need to be carefully analyzed to be able to propose new treatment options for women who experience an IBCR.

Influence of internal mammary node irradiation on long-term outcome and contralateral breast cancer incidence in node-negative breast cancer patients.

BACKGROUND AND PURPOSE: There is no general consensus concerning irradiation (RT) of internal mammary nodes (IMN) in axillary node-negative breast cancer. Based on a large series of patients treated in a single institute and followed up for a long period of time, we looked at the influence of IMN RT on late outcome of these patients as well as the development of contralateral breast cancer (CBC). PATIENTS AND METHODS: The study was based on 1630 node-negative breast cancer patients treated in our institution between 1975 and 2008 with primary conservative surgery and axillary dissection or sentinel node examination. All patients received post-operative breast RT. IMN RT was more frequent in inner or central tumours. Kaplan-Meier (K-M) overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) according to IMN RT were calculated for all patients and for patients with inner/central tumours. The K-M rate of contralateral breast cancer (CBC) was also analysed and correlated with IMN RT. RESULTS: Prognostic variables such as tumour size, histological grade, and hormone receptors were not significantly different in the groups having received IMN RT or not. Considering all patients, OS was strictly comparable in the 2 groups: 10-year values were 85% (IMN RT) and 86% (no IMN RT), respective values at 20 years were 66.6% and 61.0% (p=0.95). However, in patients presenting with inner/central tumours, OS was significantly improved in the IMN RT group with respective values of 92.5% and 87.2% at 10 years, and 80.2% and 63.3% at 20 years: Hazard ratio (HR)=0.56 (0.37-0.85); p=0.0052. Again, CSS was improved in patients with inner/central tumours having received IMN RT, with 20-year rates of 89.5% versus 79.1% in patients not receiving IMN RT (p=0.047). No difference in DFS was noticed. The actuarial rate of CBC development was comparable between patients having received IMN RT and other patients. However, considering only patients alive 10 years after primary breast surgery, the K-M rate of CBC at 20 years was 5.3% in patients without IMN RT and 7.2% in patients with such RT; HR=2.47 (1.23-4.95); p=0.008. CONCLUSIONS: IMN RT in node-negative tumours was associated with increase in OS and CSS in patients with inner or centrally located lesions. An increase in CBC development was also noticed in long-survivors of IMN RT patients; however, these findings have to be interpreted with caution because of the difference in follow-up between the 2 groups. Further studies are warranted to investigate the potential role of IMN irradiation in the development of CBC.

Phase 1 clinical trial of stereotactic body radiation therapy concomitant with neoadjuvant chemotherapy for breast cancer.

PURPOSE: Stereotactic body radiation therapy (SBRT) allows stereotactic irradiation of thoracic tumors. It may have a real impact on patients who may not otherwise qualify for breast-conserving surgery. We conducted a phase 1 trial that tested 5 dose levels of SBRT concomitant with neoadjuvant chemotherapy (NACT) before to surgery. The purpose of the current dose escalation study was to determine the maximum tolerable dose of SBRT in the treatment of breast cancer. METHODS AND MATERIALS: To define toxicity, we performed dermatologic examinations that included clinical examinations by 2 separate physicians and technical evaluations using colorimetry, dermoscopy, and skin ultrasonography. Dermatologic examinations were performed before NACT, 36 and 56 days after the beginning of NACT, and before surgery. Surgery was performed 4 to 8 weeks after the last chemotherapy session. Efficacy, the primary endpoint, was determined by the pathologic complete response (pCR) rate. RESULTS: Maximum tolerable dose was not reached. Only 1 case of dose-limiting toxicity was reported (grade 3 dermatologic toxicity), and SBRT was overall well tolerated. The pCR rate was 36%, with none being observed at the first 2 dose levels, and the highest rate being obtained at dose level 3 (25.5 Gy delivered in 3 fractions). Furthermore, the breast-conserving surgery rate was up to 92% compared with an 8% total mastectomy rate. No surgical complications were reported. CONCLUSIONS: This study demonstrates that SBRT can be safely combined with NACT. Regarding the efficacy endpoints, this trial showed promising results in terms of pCR rate (36%) and breast-conserving rate (92%). The findings provide a strong rationale for extending the study into a phase 2 trial. In view of the absence of correlation between dose and pCR, and given that the data from dose level 3 met the statistical requirements, a dose of 25.5 Gy in 3 fractions should be used for the phase 2 trial.

Dose gradient impact on equivalent dose at 2 Gy for high dose rate interstitial brachytherapy.

PURPOSE: To evaluate a new calculation model estimating the equivalent dose at 2 Gy (EQD2) taking into account dose gradient in high dose rate interstitial brachytherapy (HDRIB). MATERIAL AND METHODS: Forty dose-volume histograms (DVHs) of breast (20 pts) and prostate (20 pts) cancer dose distributions were reviewed. Physical prescribed doses (PPD) were 34 Gy (10f/5d) and 18 Gy (6f/2d) for breast (partial irradiation protocol) and prostate (boost after external irradiation) treatment, respectively. For each DVH, clinical target volume (CTV), V100, V150, V200, D90 and D100 were determined. Based on DVH segmentation, elementary doses (d) delivered to elementary volumes were determined, then multiplied by C (% of CTV receiving d). According to the linear quadratic model, EQD2 was calculated for different α/ß ratios. RESULTS: For breast implant, median EQD2 (α/ß = 4) was 42 Gy and 76 Gy (66-85) without and with dose gradient consideration, respectively. For prostate implant, median EQD2 (α/ß = 1.5) was 39 Gy and 98 Gy (90-103) whether dose gradient was not or was taken into account, respectively. CONCLUSIONS: This study pointed out that for brachytherapy, EQD2 calculation must take into account the dose gradient. Because this model is a mathematical one, it has to be cautiously applied. Nevertheless, it appears as a useful tool for EQD2 comparison between the same PPD delivered through EBRT or brachytherapy regarding trial result interpretation.

Second conservative treatment for ipsilateral breast cancer recurrence using high-dose rate interstitial brachytherapy: preliminary clinical results and evaluation of patient satisfaction.

PURPOSE: To assess early clinical results and evaluate patient satisfaction in case of second conservative treatment (2nd CT) combining lumpectomy plus high-dose rate (HDR) interstitial brachytherapy for patients (pts) presenting with ipsilateral breast cancer recurrence (IBCR). METHODS AND MATERIALS: From June 2005 to July 2009, 42 pts presenting with an IBCR underwent a second lumpectomy with intraoperative implantation of plastic tubes in the tumor bed. After performing the dose distribution analysis on the postimplant CT scan, a total dose of 34 Gy in 10 fractions over 5 consecutive days was delivered. Toxicity evaluation was based on the Common Terminology Criteria for Adverse Events v3.0 criteria. Applying a visual analogic scale (VAS) analysis, patient satisfaction regarding cosmetic result and 2nd CT possibility was performed after the end of brachytherapy. RESULTS: Median followup was 21 months (range, 6-50 months) and median age at the time of local recurrence was 65 years (range, 30-85 years). Median delay between primary and recurrence was 11 years (range, 1-35 years). Median recurrence tumor size was 12 mm (range, 2-30 mm). Median number of plastic tubes and planes were nine (range, 5-12) and two (range, 1-3), respectively. Median clinical target volume was 68 cc (range, 31.2-146 cc). Second local control rate was 97%. Twenty-two pts (60%) developed complications. Cutaneous and subcutaneous fibrosis was the most frequent side effect. Median VAS satisfaction score regarding cosmetic result was 7 of 10 (range, 4-9), whereas median VAS satisfaction score for 2nd CT was 10 of 10 (range, 8-10). CONCLUSION: A 2nd CT for IBCR using high-dose rate brachytherapy seems feasible with encouraging results in terms of second local control with an acceptable toxicity. Patient satisfaction regarding the possibility of second breast preservation should be considered.

Robotic stereotactic radioablation concomitant with neo-adjuvant chemotherapy for breast tumors.

PURPOSE: Robotic stereotactic radioablation (RSR) allows stereotactic irradiation of thoracic tumors; however, it has never been used for breast tumors and may have a real potential. We conducted a Phase I study, including neoadjuvant chemotherapy (NACT), a two-level dose-escalation study (6.5 Gy x 3 fractions and 7.5 Gy x 3 fractions) using RSR and breast-conserving surgery followed by conventional radiotherapy. MATERIALS AND METHODS: To define toxicity, we performed a dermatologic exam (DE) including clinical examination by two independent observers and technical examination by colorimetry, dermoscopy, and skin ultrasound. DE was performed before NACT (DE0), at 36 days (DE1), at 56 days (DE2), after the NACT treatment onset, and before surgery (DE3). Surgery was performed 4-8 weeks after the last chemotherapy session. A pathologic examination was also performed. RESULTS: There were two clinical complete responses and four clinical partial responses at D56 and D85. Maximum tolerable dose was not reached. All patients tolerated RSR with no fatigue; 2 patients presented with mild pain after the third fraction of the treatment. There was no significant toxicity measured with ultrasound and dermoscopy tests. Postoperative irradiation (50 Gy) has been delivered without toxicity. CONCLUSION: The study showed the feasibility of irradiation with RSR combined with chemotherapy and surgery for breast tumors. There was no skin toxicity at a dose of 19.5 Gy or 22.5 Gy delivered in three fractions combined with chemotherapy. Lack of toxicity suggested that the dose could be increased further. Pathologic response was acceptable.

[Influence of the delay between conservative surgery and radiation therapy on local relapse in node-positive breast tumor]. / Rôle du délai chirurgie conservatrice-radiothérapie sur les rechutes locales du cancer du sein avec envahissement ganglionnaire.

It has been shown that a delay in radiotherapy (RT) initiation resulted in a higher local relapse (LR) rate. The present analysis investigated retrospectively if the RT-adjuvant therapy sequence modified local-disease-free survival (L-DFS) after breast-conserving surgery (BCS) in node-positive (N +) breast cancer patients. Among seven French Adjuvant Study Group trials, 1,831 patients were assessable: 475 received RT directly after BCS, 567 after the 3rd chemotherapy (CT) cycle, and 789 after the 6th CT cycle. In the 1,356 patients receiving CT, it consisted of FEC regimens (fluorouracil, epirubicin, cyclophosphamide) in 83.5% of patients. After a 102-month median follow-up, 214 patients (11.7%) developed LR. The 9-year L-DFS rates were 92.0%, 81.5%, and 87.4%, respectively (p < 0.0001). In the multivariate analysis, the timing of RT was not associated with a higher rate of LR, whereas tumor size and hormonotherapy were prognostic factors. In our population, there was no increase in the risk of LR when RT was delayed to deliver adjuvant CT. Prognostic factors were tumor size, and hormonotherapy. The number of CT courses could modify this risk.

Influence of the time between surgery and radiotherapy on local recurrence in patients with lymph node-positive, early-stage, invasive breast carcinoma undergoing breast-conserving surgery: results of the French Adjuvant Study Group.

BACKGROUND: Radiotherapy (RT) after breast-conserving surgery (BCS) has produced significant reductions in ipsilateral breast carcinoma (BC) recurrence. It was shown previously that a delay in the initiation of RT resulted in a higher local recurrence (LR) rate. In the current retrospective analysis, the authors investigated whether the RT-adjuvant therapy sequence modified local-disease-free survival (L-DFS) after BCS in patients with early-stage, lymph node-positive BC. METHODS: Among 7 French Adjuvant Study Group trials, 1831 patients were assessable, including 475 patients who received RT directly after BCS (95 patients received no adjuvant therapy, and 380 patients received hormone therapy), 567 patients who received RT after the third chemotherapy (CT) cycle (250 patients received 1-3 courses, and 317 patients received 4-6 courses), and 789 patients received RT after the sixth CT cycle. In the 1356 patients who received CT, the regimens consisted of fluorouracil 500 mg/m(2); epirubicin 50 mg/m(2), 75 mg/m(2), or 100 mg/m(2); and cyclophosphamide 500 mg/m(2) in 83.5% of patients. RESULTS: After a median follow-up of 102 months, 214 patients (11.7%) developed LR. The 9-year L-DFS rates were 92.0%, 81.5%, and 87.4%, respectively (P < 0.0001). It was worse in patients who received 1-3 CT cycles (P = 0.02). Patients who received hormone therapy were less likely to develop LR (P = 0.02). In the multivariate analysis, the timing of RT was not associated with a higher rate of LR, whereas tumor size > 2 cm and no hormone therapy were prognostic factors. CONCLUSIONS: In the study population, there was no increase in the risk of LR when RT was delayed to deliver adjuvant CT. Prognostic factors were tumor size, and hormone therapy. The number of CT courses could modified this risk.