Intraoperative Radiotherapy (IORT) as a Boost in Patients with Early-Stage Breast Cancer – Acute Toxicity

Kraus-Tiefenbacher, U.; Bauer, L.; Kehrer, Tanja; Hermann, Brigitte; Melchert, F.; Wenz, Frederik

doi:10.1159/000091160

Cited by 42 publications

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“…The clinicopathological rationale, the technology of the device, surgical technique (fi gure 1), radiobiology, and acute and long-term toxicity have been previously described. 5,[14][15][16][17][18][19][20][21][22][23][24] Briefl y, the Intrabeam device provides a point source of low energy x-rays (50 kV maximum) at the tip of a 3·2 mm diameter tube that is placed at the centre of a spherical tumour bed applicator. After surgically positioning the appropriately sized applicator in the tumour bed, radiation is switched on for 20-35 min to target the tissues that are at highest risk of local recurrence.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2010

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SummaryBackground 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.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2010

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“…We had also ascertained that the combination of TARGIT and EBRT is safe, as tested in a 25-patient pilot study in UCL, London. 22,27 In fact, giving TARGIT at the time of surgery as a tumour bed boost followed by subsequent EBRT has been found to result in a very low 5-year recurrence rate of 1.73%, 27,28 with favourable toxicity and cosmetic outcome results; [29][30][31][32] furthermore, mathematical models of TARGIT have recently suggested that it could be superior in terms of local control to conventional radiotherapy. 33,34 This could be because of the radiotherapy limiting breast cancer cell proliferation normally caused by the trauma of surgery.…”

Section: Introductionmentioning

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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“…Surgical complications are reported at similar rates in series in the literature (5-8%). Kraus et al (17) reported the potential problems in the first months as hematoma, cellulitis, and fat necrosis, while late complications after 1 year are reported to be due to radiation (5,16).…”

Section: Discussionmentioning

confidence: 99%

Our intraoperative boost radiotherapy experience and applications

Günay

Alan

Yalçın

et al. 2016

UCD

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INTRODUCTIONBreast conserving surgery (BCS) and radiotherapy (RT) has been the standard treatment in breast cancer therapy in appropriate cases, as a result of studies and improvements achieved especially within the last 30 years. Due to the high likelihood of recurrence rates if adjuvant RT is not applied, postoperative boost RT is applied to the tumor bed (1-3).Whole breast irradiation (WBI) performed as an adjuvant therapy and again boost RT effectively controls the primary tumor site and the around of 1-2 cm where recurrence is the most common. However, in the postoperative treatment plan after pathologic examination sometimes the timing of chemotherapy (CT) (RT-CT sequence) and sometimes the location of the tumor bed are subject to change (4). This situation may result in detrimental results in terms of tumor recurrence. It is reported that intraoperative boost radiotherapy (IObRT) effectively reduces the likelihood of local recurrence as compared to adjuvant boost RT, and generates a significant difference (5, 6). Thanks to this effect of IObRT, WBI may possibly be performed later giving chemotherapy a priority.Intraoperative boost radiotherapy is beneficial to the hospital both for the treatment of a particular patient and for the treatment of other patients being treated in the same center by enabling more time and improving service quality. MATERIAL AND METHODS Case Selection CriteriaPatients who were suitable for IObRT have been selected as a candidate in our hospital's breast council within breast cancer patients who were planned to undergo BCS. In this selection, the histologic features of the tumor, if the breast tissue will allow the required flap thickness to be created surgically, if it is fatty or pendular were taken into consideration. All patients under 60 years of age were regarded as candidates if their breast tissue complied with the above-mentioned features. Tumors smaller than 3 cm in diameter, clinical and radiologic N0 patients, those without an identified BRCA1 and/or 2 mutation, those with a high likelihood of local recurrence according to histopathologic variables, patients with invasive ductal carcinoma histologic and nuclear grade 2-3 were chosen as a espetially. The selection Objective: To present our experience since November 2013, and case selection criteria for intraoperative boost radiotherapy (IObRT) that significantly reduces the local recurrence rate after breast conserving surgery in patients with breast cancer. Material and Methods:Patients who were suitable for IObRT were identified within the group of patients who were selected for breast conserving surgery at our breast council. A MOBETRON (mobile linear accelerator for IObRT) was used for IObRt during surgery. Results:Patients younger than 60 years old with <3 cm invasive ductal cancer in one focus (or two foci within 2 cm), with a histologic grade of 2-3, and a high possibility of local recurrence were admitted for IObRT application. Informed consent was obtained from all participants. Lumpectomy and sentinel lymph n...

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Intraoperative Radiotherapy (IORT) as a Boost in Patients with Early-Stage Breast Cancer – Acute Toxicity

Cited by 42 publications

References 31 publications

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

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

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)

Our intraoperative boost radiotherapy experience and applications

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