Efficacy of targeted intraoperative radiotherapy (Targit) boost after breast-conserving surgery: Updated results

Vaidya, JS; Baum, M; Tobias, JS; Massarut, Samuele; Wenz, Frederik; Hilaris, B.S.; Corica, Tammy; Kraus-Tiefenbacher, U.; Roncadin, M.; Keshtgar, Mohammed; Saunders, C.; Joseph, Deepa

doi:10.1200/jco.2008.26.15_suppl.565

Cited by 4 publications

(5 citation statements)

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“…These cells may survive fractionated radiotherapy but may not be able to survive the relatively high dose delivered locally, potentially yielding a superior result. Results from both models concur with clinical data from a large pilot series of 300 patients who received a TARGIT boost and achieved a very low local recurrence rate (1.52% actuarial at 5 years), far below that expected for that average risk population (2,3).…”

supporting

confidence: 72%

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Beneficial Effects of Intraoperative Radiotherapy on Tumor Microenvironment Could Improve Outcomes (Int J Radiat Oncol Biol Phys 2008;72:1575–1581)

Vaidya

Baldassarre

Massarut

2009

International Journal of Radiation Oncology*Biology*Physics

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supporting

confidence: 72%

“…Belletti et al (2) convincingly demonstrated that intraoperative radiotherapy (IORT) with Intrabeam can inhibit growth stimulation by wound fluid from patients undergoing breast-conserving surgery. These biological effects on the microenvironment are not included in our model (1) because up to now, no quantitation of these novel effects has been published.…”

mentioning

confidence: 99%

Beneficial Effects of Intraoperative Radiotherapy on Tumor Microenvironment Could Improve Outcomes (Int J Radiat Oncol Biol Phys 2008;72:1575–1581)

Vaidya

Baldassarre

Massarut

2009

International Journal of Radiation Oncology*Biology*Physics

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“…The protocol specified that similar surgical techniques should be employed in all patients regardless of randomisation, wound closure should be performed meticulously (air and water tight) as described [22][23][24] and sutures (if non-absorbable) should remain in place for 14 days. In our pilot study of 300 patients 27,28,39 we had found that, with the meticulous wound closure specified, wound healing was not a problem whether TARGIT was delivered during the primary surgery or as a secondary procedure.…”

Section: Surgerymentioning

confidence: 99%

An international randomised controlled trial to compare TARGeted Intraoperative radioTherapy (TARGIT) with conventional postoperative radiotherapy after breast-conserving surgery for women with early-stage breast cancer (the TARGIT-A trial)

Vaidya

Wenz

Bulsara

et al. 2016

Health Technol Assess

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BackgroundBased on our laboratory work and clinical trials we hypothesised that radiotherapy after lumpectomy for breast cancer could be restricted to the tumour bed. In collaboration with the industry we developed a new radiotherapy device and a new surgical operation for delivering single-dose radiation to the tumour bed – the tissues at highest risk of local recurrence. We named it TARGeted Intraoperative radioTherapy (TARGIT). From 1998 we confirmed its feasibility and safety in pilot studies.ObjectiveTo compare TARGIT within a risk-adapted approach with whole-breast external beam radiotherapy (EBRT) over several weeks.DesignThe TARGeted Intraoperative radioTherapy Alone (TARGIT-A) trial was a pragmatic, prospective, international, multicentre, non-inferiority, non-blinded, randomised (1 : 1 ratio) clinical trial. Originally, randomisation occurredbeforeinitial lumpectomy (prepathology) and, if allocated TARGIT, the patient received it during the lumpectomy. Subsequently, the postpathology stratum was added in which randomisation occurredafterinitial lumpectomy, allowing potentially easier logistics and a more stringent case selection, but which needed a reoperation to reopen the wound to give TARGIT as a delayed procedure. The risk-adapted approach meant that, in the experimental arm, if pre-specified unsuspected adverse factors were found postoperatively after receiving TARGIT, EBRT was recommended. Pragmatically, this reflected how TARGIT would be practised in the real world.SettingThirty-three centres in 11 countries.ParticipantsWomen who were aged ≥ 45 years with unifocal invasive ductal carcinoma preferably ≤ 3.5 cm in size.InterventionsTARGIT within a risk-adapted approach and whole-breast EBRT.Main outcome measuresThe primary outcome measure was absolute difference in local recurrence, with a non-inferiority margin of 2.5%. Secondary outcome measures included toxicity and breast cancer-specific and non-breast-cancer mortality.ResultsIn total, 3451 patients were recruited between March 2000 and June 2012. The following values are 5-year Kaplan–Meier rates for TARGIT compared with EBRT. There was no statistically significant difference in local recurrence between TARGIT and EBRT. TARGIT was non-inferior to EBRT overall [TARGIT 3.3%, 95% confidence interval (CI) 2.1% to 5.1% vs. EBRT 1.3%, 95% CI 0.7% to 2.5%;p = 0.04; Pnon-inferiority = 0.00000012] and in the prepathology stratum (n = 2298) when TARGIT was given concurrently with lumpectomy (TARGIT 2.1%, 95% CI 1.1% to 4.2% vs. EBRT 1.1%, 95% CI 0.5% to 2.5%;p = 0.31; Pnon-inferiority = 0.0000000013). With delayed TARGIT postpathology (n = 1153), the between-group difference was larger than 2.5% and non-inferiority was not established for this stratum (TARGIT 5.4%, 95% CI 3.0% to 9.7% vs. EBRT 1.7%, 95% CI 0.6% to 4.9%;p = 0.069; Pnon-inferiority = 0.06640]. The local recurrence-free survival was 93.9% (95% CI 90.9% to 95.9%) when TARGIT was given with lumpectomy compared with 92.5% (95% CI 89.7% to 94.6%) for EBRT (p = 0.35). In a planned subgroup analysis, progesterone receptor (PgR) status was found to be the only predictor of outcome: hormone-responsive patients (PgR positive) had similar 5-year local recurrence with TARGIT during lumpectomy (1.4%, 95% CI 0.5% to 3.9%) as with EBRT (1.2%, 95% CI 0.5% to 2.9%;p = 0.77). Grade 3 or 4 radiotherapy toxicity was significantly reduced with TARGIT. Overall, breast cancer mortality was much the same between groups (TARGIT 2.6%, 95% CI 1.5% to 4.3% vs. EBRT 1.9%, 95% CI 1.1% to 3.2%;p = 0.56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1.4%, 95% CI 0.8% to 2.5% vs. 3.5%, 95% CI 2.3% to 5.2%;p = 0.0086), attributable to fewer deaths from cardiovascular causes and other cancers, leading to a trend in reduced overall mortality in the TARGIT arm (3.9%, 95% CI 2.7% to 5.8% vs. 5.3%, 95% CI 3.9% to 7.3%;p = 0.099]. Health economic analyses suggest that TARGIT was statistically significantly less costly than EBRT, produced similar quality-adjusted life-years, had a positive incremental net monetary benefit that was borderline statistically significantly different from zero and had a probability of > 90% of being cost-effective. There appears to be little uncertainty in the point estimates, based on deterministic and probabilistic sensitivity analyses. If TARGIT were given instead of EBRT in suitable patients, it might potentially reduce costs to the health-care providers in the UK by £8–9.1 million each year. This does not include environmental, patient and societal costs.LimitationsThe number of local recurrences is small but the number of events for local recurrence-free survival is not as small (TARGIT 57 vs. EBRT 59); occurrence of so few events (< 3.5%) also implies that both treatments are effective and any difference is unlikely to be large. Not all 3451 patients were followed up for 5 years; however, more than the number of patients required to answer the main trial question (n = 585) were followed up for > 5 years.ConclusionsFor patients with breast cancer (women who are aged ≥ 45 years with hormone-sensitive invasive ductal carcinoma that is up to 3.5 cm in size), TARGIT concurrent with lumpectomy within a risk-adapted approach is as effective as, safer than and less expensive than postoperative EBRT.Future workThe analyses will be repeated with longer follow-up. Although this may not change the primary result, the larger number of events may confirm the effect on overall mortality and allow more detailed subgroup analyses. The TARGeted Intraoperative radioTherapy Boost (TARGIT-B) trial is testing whether or not a tumour bed boost given intraoperatively (TARGIT) boost is superior to a tumour bed boost given as part of postoperative EBRT.Trial registrationCurrent Controlled Trials ISRCTN34086741 and ClinicalTrials.gov NCT00983684.FundingUniversity College London Hospitals (UCLH)/University College London (UCL) Comprehensive Biomedical Research Centre, UCLH Charities, Ninewells Cancer Campaign, National Health and Medical Research Council and German Federal Ministry of Education and Research (BMBF). From September 2009 this project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 73. See the NIHR Journals Library website for further project information.

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“…Subsequently, a pilot study in August 2008, conducted by our colleagues in Milan on 101 patients, also confirmed low recurrence rate after a median follow-up of 36 months (five patients [0.5%] developed a local recurrence and three (0.3%) developed ipsilateral breast cancer) [19][20][21][22].…”

Section: Evidencementioning

confidence: 85%

“…We have established the safety and tolerability of the technique in Phase II studies [20,21]. In 2008, we conducted a pilot study (targeted intraoperative radiotherapy [TARGIT]) on 299 patients (with 300 cancers) who underwent BCS for their breast cancer management.…”

Section: Evidencementioning

confidence: 99%

A New Approach to Treating Breast Cancer Combining Tumor Removal and Intraoperative Radiotherapy: Is it Viable?

Keshtgar

Baum

2010

Womens Health (Lond Engl)

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Efficacy of targeted intraoperative radiotherapy (Targit) boost after breast-conserving surgery: Updated results

Cited by 4 publications

References 0 publications

Beneficial Effects of Intraoperative Radiotherapy on Tumor Microenvironment Could Improve Outcomes (Int J Radiat Oncol Biol Phys 2008;72:1575–1581)

Beneficial Effects of Intraoperative Radiotherapy on Tumor Microenvironment Could Improve Outcomes (Int J Radiat Oncol Biol Phys 2008;72:1575–1581)

An international randomised controlled trial to compare TARGeted Intraoperative radioTherapy (TARGIT) with conventional postoperative radiotherapy after breast-conserving surgery for women with early-stage breast cancer (the TARGIT-A trial)

A New Approach to Treating Breast Cancer Combining Tumor Removal and Intraoperative Radiotherapy: Is it Viable?

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