Whole-breast External Beam Radiotherapy Research Articles

Comparison of mammographic findings after intraoperative radiotherapy or external beam whole breast radiotherapy

The TARGIT (TARGeted Intraoperative Radiotherapy) trial was designed to compare local recurrence and complication rates in breast cancer patients, prospectively randomised to either EBRT (external beam whole breast radiotherapy) or a single dose of IORT (intraoperative radiotherapy). The aim of our study was to compare follow-up mammographic findings, ultrasound and biopsy rates in each group. Follow-up imaging and breast biopsies of women from one centre participating in the TARGIT-A trial were independently reviewed by two radiologists blinded to the radiotherapy treatment received. The cohort consisted of 141 patients (EBRT n = 80/IORT n = 61). There was no significant difference in the patient or disease characteristics of the two groups. The number of follow-up mammograms and length of follow-up was similar (EBRT/IORT n = 2.0/2.4; 4.3yr/5.1yr; p = 0.386 χ(2) test). There were no significant differences in mammographic scar or calcification appearances of the post-operative site. Generalised increase in breast density and skin thickening were more common in the EBRT compared to the IORT group (p = 0.002; p = 0.030, χ(2) test respectively). A trend towards additional ultrasound at follow-up was observed in the IORT group (15 of 61 [24.6%] versus 11 of 80 [13.8%]), however this was not statistically significant (p = 0.100 χ(2) test). No disease recurrence was demonstrated on any of the breast biopsies taken. Only one biopsy was reported as fat necrosis in the IORT group. Mammographic changes were more common following EBRT, although more additional follow-up ultrasounds were performed in the IORT group. IORT is not detrimental to subsequent radiological follow up.

Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial

The TARGIT-A trial compared risk-adapted radiotherapy using single-dose targeted intraoperative radiotherapy (TARGIT) versus fractionated external beam radiotherapy (EBRT) for breast cancer. We report 5-year results for local recurrence and the first analysis of overall survival. TARGIT-A was a randomised, non-inferiority trial. Women aged 45 years and older with invasive ductal carcinoma were enrolled and randomly assigned in a 1:1 ratio to receive TARGIT or whole-breast EBRT, with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy: randomisation occurred either before lumpectomy (prepathology stratum, TARGIT concurrent with lumpectomy) or after lumpectomy (postpathology stratum, TARGIT given subsequently by reopening the wound). Patients in the TARGIT group received supplemental EBRT (excluding a boost) if unforeseen adverse features were detected on final pathology, thus radiotherapy was risk-adapted. The primary outcome was absolute difference in local recurrence in the conserved breast, with a prespecified non-inferiority margin of 2·5% at 5 years; prespecified analyses included outcomes as per timing of randomisation in relation to lumpectomy. Secondary outcomes included complications and mortality. This study is registered with ClinicalTrials.gov, number NCT00983684. Patients were enrolled at 33 centres in 11 countries, between March 24, 2000, and June 25, 2012. 1721 patients were randomised to TARGIT and 1730 to EBRT. Supplemental EBRT after TARGIT was necessary in 15·2% [239 of 1571] of patients who received TARGIT (21·6% prepathology, 3·6% postpathology). 3451 patients had a median follow-up of 2 years and 5 months (IQR 12-52 months), 2020 of 4 years, and 1222 of 5 years. The 5-year risk for local recurrence in the conserved breast was 3·3% (95% CI 2·1-5·1) for TARGIT versus 1·3% (0·7-2·5) for EBRT (p=0·042). TARGIT concurrently with lumpectomy (prepathology, n=2298) had much the same results as EBRT: 2·1% (1·1-4·2) versus 1·1% (0·5-2·5; p=0·31). With delayed TARGIT (postpathology, n=1153) the between-group difference was larger than 2·5% (TARGIT 5·4% [3·0-9·7] vs EBRT 1·7% [0·6-4·9]; p=0·069). Overall, breast cancer mortality was much the same between groups (2·6% [1·5-4·3] for TARGIT vs 1·9% [1·1-3·2] for EBRT; p=0·56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1·4% [0·8-2·5] vs 3·5% [2·3-5·2]; p=0·0086), attributable to fewer deaths from cardiovascular causes and other cancers. Overall mortality was 3·9% (2·7-5·8) for TARGIT versus 5·3% (3·9-7·3) for EBRT (p=0·099). Wound-related complications were much the same between groups but grade 3 or 4 skin complications were significantly reduced with TARGIT (four of 1720 vs 13 of 1731, p=0·029). TARGIT concurrent with lumpectomy within a risk-adapted approach should be considered as an option for eligible patients with breast cancer carefully selected as per the TARGIT-A trial protocol, as an alternative to postoperative EBRT. University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre, UCLH Charities, National Institute for Health Research Health Technology Assessment programme, Ninewells Cancer Campaign, National Health and Medical Research Council, and German Federal Ministry of Education and Research.

Cosmetic outcome after intraoperative radiotherapy or external beam radiotherapy for early breast cancer: An objective assessment of patients from a randomized controlled trial.

59 Background: The international randomised contolled TARGeted Intraoperative radioTherapy (TARGIT) trial has demonstrated non-inferiority between the novel technique of TARGIT (intra-operative radiotherapy with Intrabeam) and conventional whole-breast external beam radiotherapy (EBRT) in women with early breast cancer, in terms of the primary outcome measure of risk of local relapse within the treated breast. With very low recurrence rates, cosmesis becomes an increasingly important outcome of breast conserving treatment with both surgery and radiotherapy. This study was performed to determine if the single high dose of TARGIT leads to impaired cosmesis. Methods: A validated, objective assessment tool for evaluation of cosmetic outcome was used. Frontal digital photographs were taken at baseline (before TARGIT or EBRT) and yearly thereafter for up to five years. The photographs were analysed by BCCT.core software which produces a composite score based on symmetry, colour and scar. Results: 342 patients were assessed, all over 50 years old with a median age at baseline of 64 years (IQR 59 to 68). The scores were dichotomised into Excellent and Good (EG), and Fair and Poor (FP). There were statistically significant increases in the odds of having an outcome of EG for patients in the TARGIT group relative to the EBRT group at year 1 (OR = 2.07, 95% CI 1.12 to 3.85, p = 0.021) and year 2 (OR = 2.11, 95% CI 1.0 to 4.45, p = 0.05). Conclusions: Following an objective assessment of aesthetic outcome in patients from a randomised setting, this study demonstrates that those treated with targeted intraoperative radiotherapy have a superior cosmetic result compared with those patients who received conventional whole-breast external beam radiotherapy.

Cosmetic outcome after intraoperative radiotherapy or external beam radiotherapy for early breast cancer: An objective assessment of patients from a randomized controlled trial.

1110 Background: The international randomised contolled TARGeted Intraoperative radioTherapy (TARGIT) trial has demonstrated non-inferiority between the novel technique of TARGIT (intra-operative radiotherapy with Intrabeam) and conventional whole-breast external beam radiotherapy (EBRT) in women with early breast cancer, in terms of the primary outcome measure of risk of local relapse within the treated breast. With very low recurrence rates, cosmesis becomes an increasingly important outcome of breast conserving treatment with both surgery and radiotherapy. This study was performed to determine if the single high dose of TARGIT leads to impaired cosmesis. Methods: A validated, objective assessment tool for evaluation of cosmetic outcome was used. Frontal digital photographs were taken at baseline (before TARGIT or EBRT) and yearly thereafter for up to five years. The photographs were analysed by BCCT.core software which produces a composite score based on symmetry, colour and scar. Results: 342 patients were assessed, all over 50 years old with a median age at baseline of 64 years (IQR 59 to 68). The scores were dichotomised into Excellent and Good (EG), and Fair and Poor (FP). There were statistically significant increases in the odds of having an outcome of EG for patients in the TARGIT group relative to the EBRT group at year 1 (OR = 2.07, 95%CI 1.12 to 3.85, p = 0.021) and year 2 (OR = 2.11, 95%CI 1.0 to 4.45, p = 0.05). Conclusions: Following an objective assessment of aesthetic outcome in patients from a randomised setting, this study demonstrates that those treated with targeted intraoperative radiotherapy have a superior cosmetic result compared with those patients who received conventional whole-breast external beam radiotherapy.

Mammographic findings and rates of ultrasound and biopsy following wide local excision for breast cancer in patients treated with intraoperative radiotherapy (IORT) versus external beam whole breast radiotherapy (EBRT)

Introduction: As part of the TARGIT-A trial, breast cancer patients were prospectively randomised to either EBRT or a single dose of IORT, with comparable results in local recurrence and complication rates. Our aim was to compare follow-up mammographic findings and rates of adjunctive ultrasound and biopsy between the two groups.

MammoSite partial breast irradiation following breast-conserving surgery for early-stage breast cancer.

122 Background: Partial breast irradiation (PBI) remains investigational until comparisons to whole-breast external beam radiotherapy (EBRT) confirm noninferiority. Methods: From 2004 to 2010, 103 patients at York Cancer Center (Pennsylvania) who underwent margin-negative breast-conserving surgery for early-stage invasive or in situ breast carcinoma were enrolled on a prospective MammoSite PBI protocol. NSABP B39 stage and planning criteria were utilized, with unicentric tumors up to 3 cm and pN0-1 axillary staging for invasive carcinomas. PBI was prescribed to 1 cm from the applicator surface in 10 twice-daily fractions to 34 Gy. Results: With a median follow-up of 27 months, three patients experienced recurrence: one with isolated local in-breast tumor recurrence (local IBTR), one with IBTR remote from the surgical cavity (non-local IBTR) plus regional and distant recurrence, and one with regional and distant recurrence only 3- and 5-year freedom from local IBTR are 100% and 96% (non-local IBTR: 100% and 95%). Physician-reported cosmesis evaluations are available for 25 patients at 2-3 years after treatment, with a median score of “excellent.” 26 additional patients on protocol underwent insertion of the MammoSite applicator but had it removed without treatment, most commonly due to unsatisfactory cavity conformance (24 patients), uncommonly due to infection or seroma (two patients). Their characteristics (invasive vs. in situ disease, T/N stage, negative vs. close margins, age) were not statistically different than the 103 MammoSite-treated patients. All except one received EBRT, and none experienced IBTR, which is not statistically different than the IBTR rates of the 103 MammoSite-treated patients (p=0.84). Conclusions: MammoSite PBI in well-selected patients was associated with low rates of IBTR and not significantly different than a comparison cohort selected for MammoSite PBI but treated instead with EBRT. Randomized comparisons of PBI vs. EBRT are required to confirm PBI as standard.

Long-Term Results of Targeted Intraoperative Radiotherapy (Targit) Boost During Breast-Conserving Surgery

We have previously shown that delivering targeted radiotherapy to the tumour bed intraoperatively is feasible and desirable. In this study, we report on the feasibility, safety, and long-term efficacy of TARGeted Intraoperative radioTherapy (Targit), using the Intrabeam system. A total of 300 cancers in 299 unselected patients underwent breast-conserving surgery and Targit as a boost to the tumor bed. After lumpectomy, a single dose of 20 Gy was delivered intraoperatively. Postoperative external beam whole-breast radiotherapy excluded the usual boost. We also performed a novel individualized case control (ICC) analysis that computed the expected recurrences for the cohort by estimating the risk of recurrence for each patient using their characteristics and follow-up period. The treatment was well tolerated. The median follow up was 60.5 months (range, 10-122 months). Eight patients have had ipsilateral recurrence: 5-year Kaplan Meier estimate for ipsilateral recurrence is 1.73% (SE 0.77), which compares well with that seen in the boosted patients in the European Organization for Research and Treatment of Cancer study (4.3%) and the UK STAndardisation of breast RadioTherapy study (2.8%). In a novel ICC analysis of 242 of the patients, we estimated that there should be 11.4 recurrences; in this group, only 6 recurrences were observed. Lumpectomy and Targit boost combined with external beam radiotherapy results in a low local recurrence rate in a standard risk patient population. Accurate localization and the immediacy of the treatment that has a favorable effect on tumour microenvironment may contribute to this effect. These long-term data establish the long-term safety and efficacy of the Targit technique and generate the hypothesis that Targit boost might be superior to an external beam boost in its efficacy and justifies a randomized trial.

Partial breast irradiation: a review of techniques and indications

The addition of whole-breast external beam radiotherapy (EBRT) to breast-conserving surgery results in a significant reduction in the risk of death due to breast cancer, but this may be offset by an increase in deaths from other causes and toxicity to surrounding organs. Because of this, and with a view to patterns of local recurrence, irradiation of the tumour bed has been explored in selected patients with early breast cancer using a variety of radiotherapeutic modalities. This review article explores the treatment options for partial breast irradiation and examines their role within the field of breast cancer treatment.

Intraoperative radiotherapy (IORT) as a boost during breast conserving surgery (BCS) using low kV X-rays: The first 5 years of experience with a novel approach

626 Background: Recently, the concept of IORT during BCS has been introduced using linear accelerators, brachytherapy or dedicated mobile IORT devices generating fast electrons or low energy X-rays. Here, we report the first 5 years of a single center experience after introduction of a novel approach to deliver IORT as a tumor bed boost during BCS for breast cancer. Methods: 155 breast cancers in 154 women (median age 63 yrs, range 30 - 83 yrs, T1/T2 = 110/45, N0/N+ = 104/51) were treated between February 2002 and December 2007 at the University Medical Center Mannheim/University of Heidelberg, in whom IORT as tumor bed boost was applied using 50 kV X rays (20 Gy, INTRABEAM, Carl Zeiss Oberkochen, additional OR time about 45 - 60 min) followed by 46 - 50 Gy external beam whole breast radiotherapy (EBRT). Chemotherapy was given before EBRT. The median interval between BCS+IORT and EBRT was 10 wks. Median follow-up was 34 mon (max 79.6 mon, 1 pt lost to f/u). Overall survival (OS), local relapse free survival (LRFS) and disease free survival (DFS) were calculated at 5 yrs using the Kaplan Meier method. 81 patients were evaluated at 3 yr f/u for normal tissue effects using the LENT SOMA scoring system. Results: Ten patients have died, 2 pts suffered from in breast relapse and 8 pts developed distant metastases yielding a 5yr OS of 87.0%, a 5yr LRFS of 98.4% and a 5 yr DFS of 73.9%. Grade 3 fibroses of the tumor bed were detected in 6% of the patients after 3 yrs. Skin toxicity was mild (teleangiectases and hyperpigmentations in 6% each). Conclusions: IORT as a tumor bed boost using the INTRABEAM system yields low recurrence and toxicity rates when followed by external beam whole breast radiotherapy. [Table: see text]

Dose volume histogram analysis of normal structures associated with accelerated partial breast irradiation delivered by high dose rate brachytherapy and comparison with whole breast external beam radiotherapy fields

PurposeTo assess the radiation dose delivered to the heart and ipsilateral lung during accelerated partial breast brachytherapy using a MammoSite™ applicator and compare to those produced by whole breast external beam radiotherapy (WBRT).Materials and methodsDosimetric analysis was conducted on patients receiving MammoSite breast brachytherapy following conservative surgery for invasive ductal carcinoma. Cardiac dose was evaluated for patients with left breast tumors with a CT scan encompassing the entire heart. Lung dose was evaluated for patients in whom the entire lung was scanned. The prescription dose of 3400 cGy was 1 cm from the balloon surface. MammoSite dosimetry was compared to simulated WBRT fields with and without radiobiological correction for the effects of dose and fractionation. Dose parameters such as the volume of the structure receiving 10 Gy or more (V10) and the dose received by 20 cc of the structure (D20), were calculated as well as the maximum and mean doses received.ResultsFifteen patients were studied, five had complete lung data and six had left-sided tumors with complete cardiac data. Ipsilateral lung volumes ranged from 925–1380 cc. Cardiac volumes ranged from 337–551 cc. MammoSite resulted in a significantly lower percentage lung V30 and lung and cardiac V20 than the WBRT fields, with and without radiobiological correction.ConclusionThis study gives low values for incidental radiation received by the heart and ipsilateral lung using the MammoSite applicator. The volume of heart and lung irradiated to clinically significant levels was significantly lower with the MammoSite applicator than using simulated WBRT fields of the same CT data sets.Trial registrationDana Farber Trial Registry number 03-179