Targit information



TARGIT A Trial results

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

Author Vaidya, J. S., Wenz, F., Bulsara, M., Tobias, J. S., Joseph, D. J., Keshtgar, M., Flyger, H. L., Massarut, S., Alvarado, M., Saunders, C., Eiermann, W., Metaxas, M., Sperk, E., Sutterlin, M., Brown, D., Esserman, L., Roncadin, M., Thompson, A., Dewar, J. A., Holtveg, H. M., Pigorsch, S., Falzon, M., Harris, E., Matthews, A., Brew-Graves, C., Potyka, I., Corica, T., Williams, N. R., and Baum, M.

  • Date of Publication: 8-11-2013
  • Journal Name: Lancet


BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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.


Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial

Author Vaidya, J. S., Joseph, D. J., Tobias, J. S., Bulsara, M., Wenz, F., Saunders, C., Alvarado, M., Flyger, H. L., Massarut, S., Eiermann, W., Keshtgar, M., Dewar, J., Kraus-Tiefenbacher, U., Sutterlin, M., Esserman, L., Holtveg, H. M., Roncadin, M., Pigorsch, S., Metaxas, M., Falzon, M., Matthews, A., Corica, T., Williams, N. R., and Baum, M.

  • Date of Publication: 10-7-2010
  • Start Page: 91
  • End Page: 102
  • Journal Name: Lancet
  • Volume: 376


BACKGROUND: After breast-conserving surgery, 90% of local recurrences occur within the index quadrant despite the presence of multicentric cancers elsewhere in the breast. Thus, restriction of radiation therapy to the tumour bed during surgery might be adequate for selected patients. We compared targeted intraoperative radiotherapy with the conventional policy of whole breast external beam radiotherapy. METHODS: Having safely piloted the new technique of single-dose targeted intraoperative radiotherapy with Intrabeam, we launched the TARGIT-A trial on March 24, 2000. In this prospective, randomised, non-inferiority trial, women aged 45 years or older with invasive ductal breast carcinoma undergoing breast-conserving surgery were enrolled from 28 centres in nine countries. Patients were randomly assigned in a 1:1 ratio to receive targeted intraoperative radiotherapy or whole breast external beam radiotherapy, with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy. Neither patients nor investigators or their teams were masked to treatment assignment. Postoperative discovery of predefined factors (eg, lobular carcinoma) could trigger addition of external beam radiotherapy to targeted intraoperative radiotherapy (in an expected 15% of patients). The primary outcome was local recurrence in the conserved breast. The predefined non-inferiority margin was an absolute difference of 2.5% in the primary endpoint. All randomised patients were included in the intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT00983684. FINDINGS: 1113 patients were randomly allocated to targeted intraoperative radiotherapy and 1119 were allocated to external beam radiotherapy. Of 996 patients who received the allocated treatment in the targeted intraoperative radiotherapy group, 854 (86%) received targeted intraoperative radiotherapy only and 142 (14%) received targeted intraoperative radiotherapy plus external beam radiotherapy. 1025 (92%) patients in the external beam radiotherapy group received the allocated treatment. At 4 years, there were six local recurrences in the intraoperative radiotherapy group and five in the external beam radiotherapy group. The Kaplan-Meier estimate of local recurrence in the conserved breast at 4 years was 1.20% (95% CI 0.53-2.71) in the targeted intraoperative radiotherapy and 0.95% (0.39-2.31) in the external beam radiotherapy group (difference between groups 0.25%, -1.04 to 1.54; p=0.41). The frequency of any complications and major toxicity was similar in the two groups (for major toxicity, targeted intraoperative radiotherapy, 37 [3.3%] of 1113 vs external beam radiotherapy, 44 [3.9%] of 1119; p=0.44). Radiotherapy toxicity (Radiation Therapy Oncology Group grade 3) was lower in the targeted intraoperative radiotherapy group (six patients [0.5%]) than in the external beam radiotherapy group (23 patients [2.1%]; p=0.002). INTERPRETATION: For selected patients with early breast cancer, a single dose of radiotherapy delivered at the time of surgery by use of targeted intraoperative radiotherapy should be considered as an alternative to external beam radiotherapy delivered over several weeks.


TARGIT Boost phase II study

Long-term results of targeted intraoperative radiotherapy (Targit) boost during breast-conserving surgery

Author Vaidya, J. S., Baum, M., Tobias, J. S., Wenz, F., Massarut, S., Keshtgar, M., Hilaris, B., Saunders, C., Williams, N. R., Brew-Graves, C., Corica, T., Roncadin, M., Kraus-Tiefenbacher, U., Sutterlin, M., Bulsara, M., and Joseph, D.

  • Date of Publication: 15-11-2011
  • Start Page: 1091
  • End Page: 1097
  • Journal Name: Int.J.Radiat.Oncol.Biol.Phys.
  • Volume: 81
  • Issue: 4


PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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


TARGIT and normal tissues

An observational study using gamma-H2AX foci to investigate cardiac doses of radiation in women following adjuvant radiotherapy for breast cancer: External beam radiotherapy versus targeted intraoperative radiotherapy

Author Woolf, D. K., Williams, N. R., Bakhshi, R., Madani, Y., Fawcitt, S., Pigott, K., Short, S. C., and Keshtgar, M.

  • Date of Publication: 2013
  • Journal Name: Cancer Research
  • Volume: (in press)


Can the risk of secondary cancer induction after breast conserving therapy be reduced using intraoperative radiotherapy (IORT) with low-energy x-rays?

Author Aziz, M. H., Schneider, F., Clausen, S., Blank, E., Herskind, C., Afzal, M., and Wenz, F.

  • Date of Publication: 2011
  • Start Page: 174
  • Journal Name: Radiat.Oncol.
  • Volume: 6


BACKGROUND: Radiation induced secondary cancers are a rare but severe late effect after breast conserving therapy. Intraoperative radiotherapy (IORT) is increasingly used during breast conserving surgery. The purpose of this analysis was to estimate secondary cancer risks after IORT compared to other modalities of breast radiotherapy (A


Cost effectiveness

Cost-effectiveness analysis of intraoperative radiation therapy for early-stage breast cancer

Author Alvarado, M. D., Mohan, A. J., Esserman, L. J., Park, C. C., Harrison, B. L., Howe, R. J., Thorsen, C., and Ozanne, E. M.

  • Date of Publication: 2013
  • Start Page: 2873
  • End Page: 2880
  • Journal Name: Ann.Surg.Oncol.
  • Volume: 20
  • Issue: 9


Shortened courses of radiation therapy have been shown to be similarly effective to whole-breast external-beam radiation therapy (WB-EBRT) in terms of local control. We sought to analyze, from a societal perspective, the cost-effectiveness of two radiation strategies for early-stage invasive breast cancer: single-dose intraoperative radiation therapy (IORT) and the standard 6-week course of WB-EBRT. METHODS: We developed a Markov decision-analytic model to evaluate these treatment strategies in terms of life expectancy, quality-adjusted life years (QALYs), costs, and the incremental cost-effectiveness ratio over 10 years. RESULTS: IORT single-dose intraoperative radiation therapy was the dominant, more cost-effective strategy, providing greater quality-adjusted life years at a decreased cost compared with 6-week WB-EBRT. The model was sensitive to health state utilities and recurrence rates, but not costs. IORT was either the preferred or dominant strategy across all sensitivity analyses. The two-way sensitivity analyses demonstrate the need to accurately determine utility values for the two forms of radiation treatment and to avoid indiscriminate use of IORT. CONCLUSIONS: With less cost and greater QALYs than WB-EBRT, IORT is the more valuable strategy. IORT offers a unique example of new technology that is less costly than the current standard of care option but offers similar efficacy. Even when considering the capital investment for the equipment ($425 K, low when compared with the investments required for robotic surgery or high-dose-rate brachytherapy), which could be recouped after 3-4 years conservatively, these results support IORT as a change in practice for treating early-stage invasive breast cancer


Laboratory studies

Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding

Author Belletti, B., Vaidya, J. S., D'Andrea, S., Entschladen, F., Roncadin, M., Lovat, F., Berton, S., Perin, T., Candiani, E., Reccanello, S., Veronesi, A., Canzonieri, V., Trovo, M. G., Zaenker, K. S., Colombatti, A., Baldassarre, G., and Massarut, S.

  • Date of Publication: 1-3-2008
  • Start Page: 1325
  • End Page: 1332
  • Journal Name: Clin.Cancer Res.
  • Volume: 14
  • Issue: 5


PURPOSE: After apparently successful excision of breast cancer, risk of local recurrence remains high mainly in the area surrounding the original tumor, indicating that wound healing processes may be implicated. The proportional reduction of this risk by radiotherapy does not depend on the extent of surgery, suggesting that radiotherapy, in addition to killing tumor cells, may influence the tumor microenvironment. EXPERIMENTAL DESIGN: We studied how normal and mammary carcinoma cell growth and motility are affected by surgical wound fluids (WF), collected over 24 h following breast-conserving surgery in 45 patients, 20 of whom had received additional TARGeted Intraoperative radioTherapy (TARGIT), immediately after the surgical excision. The proteomic profile of the WF and their effects on the activation of intracellular signal transduction pathways of breast cancer cells were also analyzed. RESULTS: WF stimulated proliferation, migration, and invasion of breast cancer cell lines. The stimulatory effect was almost completely abrogated when fluids from TARGIT-treated patients were used. These fluids displayed altered expression of several cytokines and failed to properly stimulate the activation of some intracellular signal transduction pathways, when compared with fluids harvested from untreated patients. CONCLUSIONS: Delivery of TARGIT to the tumor bed alters the molecular composition and biological activity of surgical WF. This novel antitumoral effect could, at least partially, explain the very low recurrence rates found in a large pilot study using TARGIT. It also opens a novel avenue for identifying new molecular targets and testing novel therapeutic agents


TARGIT modulates miRNAs expression to control growth factors production in breast tissue

Author Belletti, B., Massarut, S., D'Andrea, S., Martinuzzo, D., Roncadin, M., Perin, T., Sartor, G., Trovo, M. G., Calin, G., and Baldassarre, G.

  • Date of Publication: 2011
  • Start Page: 262
  • Journal Name: The Breast
  • Volume: 20
  • Issue: 1
  • Date Secondary: 1-3-2011

Radiation protection

Radiation protection for an intra-operative X-ray device

Author Eaton, D. J., Gonzalez, R., Duck, S., and Keshtgar, M.

  • Date of Publication: 2011
  • Start Page: 1034
  • End Page: 1039
  • Journal Name: Br.J.Radiol.
  • Volume: 84
  • Issue: 1007


OBJECTIVES: Therapeutic partial breast irradiation can be delivered intra-operatively using the Intrabeam 50 kVp compact X-ray device. Spherical applicators are added to the source to give an isotropic radiation dose. The low energy of this unit leads to rapid attenuation with distance, but dose rates are much greater than for diagnostic procedures. METHODS: To investigate the shielding requirements for this unit, attenuation measurements were carried out with manufacturer-provided tungsten-rubber sheets, lead, plasterboard and bricks. A prospective environmental dose rate survey was also conducted in the designated theatre. RESULTS: As a result of isotropic geometry, the scattered dose around shielding can be 1% of primary and thus often dominates measured dose rates compared with transmission. The absorbed dose rate of the unshielded source at 1 m was 11.6 mGy h(-1) but this was reduced by 95% with the shielding sheets. Measured values for the common shielding materials were similar to reference data for the attenuation of a 50 kVp diagnostic X-ray beam. Two lead screens were constructed to shield operators remaining in the theatre and an air vent into a service corridor. A lead apron would also provide suitable attenuation, although a screen allows greater flexibility for treatment operators. With these measures, staff doses were reduced to negligible quantities. Survey measurements taken during patient treatments confirmed no additional measures were required, but the theatre should be a controlled area and access restricted. CONCLUSION: Results from this study and reference data can be used for planning other facilities


In vivo dosimetry for single-fraction targeted intraoperative radiotherapy (TARGIT) for breast cancer

Author Eaton, D. J., Best, B., Brew-Graves, C., Duck, S., Ghaus, T., Gonzalez, R., Pigott, K., Reynolds, C., Williams, N. R., and Keshtgar, M. R.

  • Date of Publication: 1-4-2012
  • Start Page: e819
  • End Page: e824
  • Journal Name: Int.J.Radiat.Oncol.Biol.Phys.
  • Volume: 82
  • Issue: 5


PURPOSE: In vivo dosimetry provides an independent check of delivered dose and gives confidence in the introduction or consistency of radiotherapy techniques. Single-fraction intraoperative radiotherapy of the breast can be performed with the Intrabeam compact, mobile 50 kV x-ray source (Carl Zeiss Surgical, Oberkochen, Germany). Thermoluminescent dosimeters (TLDs) can be used to estimate skin doses during these treatments. METHODS AND MATERIALS: Measurements of skin doses were taken using TLDs for 72 patients over 3 years of clinical treatments. Phantom studies were also undertaken to assess the uncertainties resulting from changes in beam quality and backscatter conditions in vivo. RESULTS: The mean measured skin dose was 2.9 +/- 1.6 Gy, with 11% of readings higher than the prescription dose of 6 Gy, but none of these patients showed increased complications. Uncertainties due to beam hardening and backscatter reduction were small compared with overall accuracy. CONCLUSIONS: TLDs are a useful and effective method to measure in vivo skin doses in intraoperative radiotherapy and are recommended for the initial validation or any modification to the delivery of this technique. They are also an effective tool to show consistent and safe delivery on a more frequent basis or to determine doses to other critical structures as required


TARGIT in special circumstances

Targeted intraoperative radiotherapy for breast cancer in patients in whom external beam radiation is not possible

Author Keshtgar, M. R., Vaidya, J. S., Tobias, J. S., Wenz, F., Joseph, D., Stacey, C., Metaxas, M. G., Keller, A., Corica, T., Williams, N. R., and Baum, M.

  • Date of Publication: 1-5-2011
  • Start Page: 31
  • End Page: 38
  • Journal Name: Int.J.Radiat.Oncol.Biol.Phys.
  • Volume: 80
  • Issue: 1


PURPOSE: External beam radiation therapy (EBRT) following wide local excision of the primary tumor is the standard treatment in early breast cancer. In some circumstances this procedure is not possible or is contraindicated or difficult. The purpose of this study was to determine the safety and efficacy of targeted intraoperative radiotherapy (TARGIT) when EBRT is not feasible. METHODS AND MATERIALS: We report our experience with TARGIT in three centers (Australia, Germany, and the United Kingdom) between 1999 and 2008. Patients at these centers received a single radiation dose of 20 Gy to the breast tissue in contact with the applicator (or 6 Gy at 1-cm distance), as they could not be given EBRT and were keen to avoid mastectomy. RESULTS: Eighty patients were treated with TARGIT. Reasons for using TARGIT were 21 patients had previously received EBRT, and 31 patients had clinical reasons such as systemic lupus erythematosus, motor neuron disease, Parkinson's disease, ankylosing spondylitis, morbid obesity, and cardiovascular or severe respiratory disease. Three of these patients received percutaneous radiotherapy without surgery; 28 patients were included for compelling personal reasons, usually on compassionate grounds. After a median follow-up of 38 months, only two local recurrences were observed, an annual local recurrence rate of 0.75% (95% confidence interval, 0.09%-2.70%). CONCLUSIONS: While we await the results of the randomized trial (over 2,000 patients have already been recruited), TARGIT is an acceptable option but only in highly selected cases that cannot be recruited in the trial and in whom EBRT is not feasible/possible


TARGIT in the presence of a pacemaker

Pacemaker and radiotherapy in breast cancer: is targeted intraoperative radiotherapy the answer in this setting?

Author Keshtgar, M. R., Eaton, D. J., Reynolds, C., Pigott, K., Davidson, T., Gauter-Fleckenstein, B., and Wenz, F.

  • Date of Publication: 2012
  • Start Page: 128
  • Journal Name: Radiat.Oncol.
  • Volume: 7


We present the case of an 83 year old woman with a cardiac pacemaker located close in distance to a subsequently diagnosed invasive ductal carcinoma of the left breast. Short range intraoperative radiotherapy was given following wide local excision and sentinel node biopsy. The challenges of using ionising radiation with pacemakers is also discussed


Cosmetic outcome

Objective assessment of cosmetic outcome after targeted intraoperative radiotherapy in breast cancer: results from a randomised controlled trial

Author Keshtgar, M. R., Williams, N. R., Bulsara, M., Saunders, C., Flyger, H., Cardoso, J. S., Corica, T., Bentzon, N., Michalopoulos, N. V., and Joseph, D. J.

  • Date of Publication: 2013
  • Start Page: 519
  • End Page: 525
  • Journal Name: Breast Cancer Res.Treat.
  • Volume: 140
  • Issue: 3


The international randomised targeted intraoperative radiotherapy (TARGIT) trial has demonstrated evidence of non-inferiority between the novel technique of TARGIT (intra-operative radiotherapy with Intrabeam((R))) and conventional 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. Cosmesis is an increasingly important outcome of breast conserving treatment with both surgery and radiotherapy contributing to this. It was unknown if the single high dose of TARGIT may lead to damaging fibrosis and thus impair cosmesis further, so we objectively evaluated the aesthetic outcome of patients within the TARGIT randomised controlled trial. We have used an objective assessment tool for evaluation of cosmetic outcome. Frontal digital photographs were taken at baseline (before TARGIT or EBRT) and yearly thereafter for up to 5 years. The photographs were analysed by BCCT.core, a validated software which produces a composite score based on symmetry, colour and scar. 342 patients were assessed, median age at baseline 64 years (IQR 59-68). 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 1.12-3.85, p = 0.021) and year 2 (OR 2.11, 95 % CI 1.0-4.45, p = 0.05). Following a totally objective assessment in a randomised setting, the aesthetic outcome of patients demonstrates that those treated with TARGIT have a superior cosmetic result to those patients who received conventional external beam radiotherapy


TARGIT for relapsed breast cancer

Intraoperative radiotherapy during a second breast-conserving procedure for relapsed breast cancer after previous external beam radiotherapy

Author Kraus-Tiefenbacher, U., Blank, E., and Wenz, F.

  • Start Page: 1279
  • End Page: 1280
  • Journal Name: Int.J.Radiat.Oncol.Biol.Phys.
  • Volume: 80
  • Issue: 4



Other uses for Intrabeam

A novel device for intravaginal electronic brachytherapy

Author Schneider, F., Fuchs, H., Lorenz, F., Steil, V., Ziglio, F., Kraus-Tiefenbacher, U., Lohr, F., and Wenz, F.

  • Date of Publication: 15-7-2009
  • Start Page: 1298
  • End Page: 1305
  • Journal Name: Int.J.Radiat.Oncol.Biol.Phys.
  • Volume: 74
  • Issue: 4


PURPOSE: Postoperative intravaginal brachytherapy for endometrial carcinoma is usually performed with (192)Ir high-dose rate (HDR) afterloading. A potential alternative is treatment with a broadband 50kV X-ray point source, the advantage being its low energy and the consequential steep dose gradient. The aim of this study was to create and evaluate a homogeneous cylindrical energy deposition around a newly designed vaginal applicator. METHODS AND MATERIALS: To create constant isodose layers along the cylindrical plastic vaginal applicator, the source (INTRABEAM system) was moved in steps of 17-19.5 mm outward from the tip of the applicator. Irradiation for a predetermined time was performed at each position. The axial shift was established by a stepping mechanism that was mounted on a table support. The total dose/dose distribution was determined using film dosimetry (Gafchromic EBT) in a "solid water" phantom. The films were evaluated with Mathematica 5.2 and OmniPro-I'mRT 1.6. The results (dose D0/D5/D10 in 0/5/10 mm tissue depth) were compared with an (192)Ir HDR afterloading plan for multiple sampling points around the applicator. RESULTS: Three different dose distributions with lengths of 3.9-7.3 cm were created. The irradiation time based on the delivery of 5/7 Gy to a 5 mm tissue depth was 19/26 min to 27/38 min. D0/D5/D10 was 150%/100%/67% for electronic brachytherapy and 140%/100%/74% for the afterloading technique. The deviation for repeated measurements in the phantom was <7%. CONCLUSIONS: It is possible to create a homogeneous cylindrical dose distribution, similar to (192)Ir HDR afterloading, through the superimposition of multiple spherical dose distributions by stepping a kilovolt point source


Intraoperative radiotherapy during kyphoplasty for vertebral metastases (Kypho-IORT): first clinical results

Author Reis, T., Schneider, F., Welzel, G., Schmidt, R., Bludau, F., Obertacke, U., and Wenz, F.

  • Date of Publication: 2012
  • Start Page: 434
  • End Page: 440
  • Journal Name: Tumori
  • Volume: 98
  • Issue: 4


AIMS AND BACKGROUND: Kyphoplasty is an effective procedure providing structural stability and pain alleviation in vertebral metastases. To prevent early regrowth, patients typically receive postoperative fractionated radiotherapy, which is associated with long treatment duration. Therefore, we established a new approach to deliver intraoperative radiotherapy during kyphoplasty to shorten the treatment time and reach structural stability and sterilization of the metastases (Kypho-IORT). METHODS AND STUDY DESIGN: For Kypho-IORT, a 50 kV X-ray source with a specially designed applicator was used. A radiation dose of 8 Gy in 5 mm distance was delivered. After radiation the device was removed and the kyphoplasty was completed according to the standard procedure. Since August 2009, 18 patients with instable or painful spinal metastases received Kypho-IORT. The median age was 63 years (range, 43-73). RESULTS: Kypho-IORT was successfully performed in 18 of 21 vertebral lesions (86%). No severe complications occurred during or early after IORT. The median pain score using a visual analogue scale decreased from 5/10 before the procedure to 2.5/10 at day 1 (P <0.001) and to 0/10 six weeks after the procedure (P = 0.001). Imaging studies were available for 15 of 18 patients. Stable disease within the irradiated vertebral body was seen in 14 patients (93%) and local progressive disease in one patient (7%). No re-irradiation due to local progressive disease or pain recurrence was necessary within the median follow-up of 4.5 months. CONCLUSIONS: Kypho-IORT is well tolerated without severe side effects and provides fast improvement of pain. Although stable disease was seen in 93% of the patients, a longer follow-up is necessary to assess the effectiveness. A dose escalation study to establish the maximally tolerated dose has been initiated


Quality of Life

Radiation-related quality of life parameters after targeted intraoperative radiotherapy versus whole breast radiotherapy in patients with breast cancer: results from the randomized phase III trial TARGIT-A

Author Welzel, G., Boch, A., Sperk, E., Hofmann, F., Kraus-Tiefenbacher, U., Gerhardt, A., Suetterlin, M., and Wenz, F.

  • Date of Publication: 7-1-2013
  • Start Page: 9
  • Journal Name: Radiat.Oncol.
  • Volume: 8
  • Issue: 1


BACKGROUND: Intraoperative radiotherapy (IORT) is a new treatment approach for early stage breast cancer. This study reports on the effects of IORT on radiation-related quality of life (QoL) parameters. METHODS: Two hundred and thirty women with stage I-III breast cancer (age, 31 to 84 years) were entered into the study. A single-center subgroup of 87 women from the two arms of the randomized phase III trial TARGIT-A (TARGeted Intra-operative radioTherapy versus whole breast radiotherapy for breast cancer) was analyzed. Furthermore, results were compared to non-randomized control groups: n = 90 receiving IORT as a tumor bed boost followed by external beam whole breast radiotherapy (EBRT) outside of TARGIT-A (IORT-boost), and n = 53 treated with EBRT followed by an external-beam boost (EBRT-boost). QoL was collected using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 (QLQ-C30) and BR23 (QLQ-BR23). The mean follow-up period in the TARGIT-A groups was 32 versus 39 months in the non-randomized control groups. RESULTS: Patients receiving IORT alone reported less general pain (21.3 points), breast (7.0 points) and arm (15.1 points) symptoms, and better role functioning (78.7 points) as patients receiving EBRT (40.9; 19.0; 32.8; and 60.5 points, respectively, P < 0.01). Patients receiving IORT alone also had fewer breast symptoms than TARGIT-A patients receiving IORT followed by EBRT for high risk features on final pathology (IORT-EBRT; 7.0 versus 29.7 points, P < 0.01). There were no significant differences between TARGIT-A patients receiving IORT-EBRT compared to non-randomized IORT-boost or EBRT-boost patients and patients receiving EBRT without a boost. CONCLUSIONS: In the randomized setting, important radiation-related QoL parameters after IORT were superior to EBRT. Non-randomized comparisons showed equivalent parameters in the IORT-EBRT group and the control groups


Patient Preference

Patient preferences regarding intraoperative versus external beam radiotherapy following breast-conserving surgery

Author Alvarado, M. D., Conolly, J., Park, C., Sakata, T., Mohan, A. J., Harrison, B. L., Hayes, M., Esserman, L. J., and Ozanne, E. M.

  • Date of Publication: 30-11-2013
  • Journal Name: Breast Cancer Res.Treat.


The TARGIT-A Trial is an international randomized, prospective trial comparing intraoperative radiotherapy (IORT) for equivalence to external beam radiotherapy (EBRT) following lumpectomy for invasive breast cancer in selected low-risk patients; early results suggest that outcomes are similar. In addition to effectiveness data and cost considerations, the preferences of patients should help inform practice. This study was undertaken to explore and quantify preference in choosing between IORT and the current standard, EBRT. Eligible subjects were current or past candidates for breast-conserving surgery and radiation being seen at the University of California, San Francisco Breast Care Center. A trade-off technique varying the risk of local recurrence for IORT was used to quantify any additional accepted risk that these patients would accept to receive either treatment. Patients were first presented with a slideshow comparing EBRT with the experimental IORT option before being asked their preferences given hypothetical 10-year local recurrence risks. Patients were then given a questionnaire on demographic, social and clinical factors. Data from 81 patients were analyzed. The median additional accepted risk to have IORT was 2.3 % (-9 to 39 %), mean 3.2 %. Only 7 patients chose to accept additional risk for EBRT; 22 accepted IORT at no additional risk; and the remaining 52 chose IORT with some additional risk. Patients weigh trade-offs of risks and benefits when presented with medical treatment choices. Our results show that the majority of breast cancer patients will accept a small increment of local risk for a simpler delivery of radiation. Further studies that incorporate outcome and side effect data from the TARGIT-A trial clarify the expected consequences of a local recurrence, and include an expanded range of radiation options that could help guide clinical decision making in this area


Patient Preferences for Adjuvant Radiotherapy in Early Breast Cancer - an Australian Sub-study of the International TARGIT Trial

Author Corica, T., Nowak, A., Saunders, C., Bulsara, M., and Joseph, D.

  • Date of Publication: 2012
  • Start Page: S187
  • Journal Name: European Journal of Cancer
  • Volume: 48, Supplement 1
  • Title Secondary: Abstract Book EBCC8 - European Breast Cancer Conference



Clinician preference

Intraoperative radiotherapy for early breast cancer: do health professionals choose convenience or risk?

Author Corica, T., Joseph, D., Saunders, C., Bulsara, M., and Nowak, A. K.

  • Date of Publication: 2014
  • Start Page: 33
  • Journal Name: Radiat.Oncol.
  • Volume: 9
  • Issue: 1


BACKGROUND: The randomized TARGIT trial comparing experimental intra-operative radiotherapy (IORT) to up to 7 weeks of daily conventional external beam radiotherapy (EBRT) recruited participants in Western Australia between 2003 and 2012. We aimed to understand preferences for this evolving radiotherapy treatment for early breast cancer (EBC) in health professionals, and how they changed over time and in response to emerging data. Preferences for single dose IORT or EBRT for EBC were elicited in 2004 and 2011, together with factors that may be associated with these preferences. METHODS: Western Australian health professionals working with breast cancer patients were invited to complete a validated, self-administered questionnaire. The questionnaire used hypothetical scenarios and trade-off methodology to determine the maximum increase in risk of local recurrence health professionals were willing to accept in order to have a single dose of IORT in the place of EBRT if they were faced with this decision themselves. RESULTS: Health professional characteristics were similar across the two time points although 2011 included a higher number of nurse (49% vs. 36%) and allied health (10% vs. 4%) participants and a lower number of radiation therapists (17% vs. 32% ) compared to 2004.Health professional preferences varied, with 7.5% and 3% judging IORT unacceptable at any risk, 18% and 21% judging IORT acceptable only if offering an equivalent risk, 56% and 59% judging IORT acceptable with a low maximum increase in risk (1-3%) and 19% and 17% judging a high maximum increase in risk acceptable (4-5%), in 2004 and 2011 respectively. A significantly greater number of nurses accepted IORT as a treatment option in 2011. CONCLUSIONS: Most Western Australian health professionals working with breast cancer patients are willing to accept an increase in risk of local recurrence in order to replace EBRT with IORT in a hypothetical setting. This finding was consistent over two time points spanning 7 years despite the duration of clinical experience with IORT and the publication of the early clinical results of IORT in 2010. These results need to be compared with preferences elicited from patient groups, and further investigation into the impact of personal preferences on health professionals' advice to patients is warranted


Review articles

Intraoperative radiotherapy in the treatment of breast cancer: a review of the evidence

Author Williams, N. R., Pigott, K. H., and Keshtgar, M. R.

  • Date of Publication: 2011
  • Start Page: 375170
  • Journal Name: Int.J.Breast Cancer
  • Volume: 2011


The surgical treatment of early breast cancer has evolved from the removal of the entire breast and surrounding tissues (mastectomy) to the removal of the tumour together with a margin of healthy tissue (lumpectomy). Adjuvant radiotherapy, however, is still mainly given to the whole breast. Furthermore, external beam radiotherapy is often given several months after initial surgery and requires the patient to attend the radiotherapy centre daily for several weeks. A single fraction of radiotherapy given during surgery directly to the tumour bed (intraoperative radiotherapy) avoids these problems. The rationale and level-1 evidence for the safety and efficacy of the technique are reviewed


Current status and advances in management of early breast cancer

Author Keshtgar, M., Davidson, T., Pigott, K., Falzon, M., and Jones, A.

  • Date of Publication: 2010
  • Start Page: 199
  • End Page: 202
  • Journal Name: Int.J.Surg.
  • Volume: 8
  • Issue: 3


Breast cancer is the most common female cancer. Worldwide, more than a million women are diagnosed every year. However despite this increase, the mortality rate is declining. This is due to combination of factors including early diagnosis and effective treatment. This manuscript which is presented in two sections outlines the current status in management of early breast cancer. Section 1 focuses on the advances in diagnosis and surgical treatment of breast cancer and give an overview of the histopathological aspects. The focus of section 2 is on advances on adjuvant treatment of breast cancer including radiotherapy, chemotherapy and endocrine treatment