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Accelerated partial breast irradiation with perioperative multicatheter interstitial brachytherapy—A feasibility study
Brachytherapy
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(2018)
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Accelerated partial breast irradiation with perioperative multicatheter interstitial brachytherapydA feasibility study Denisa Pohankova1, Igor Sirak1,*, Pavel Jandık2, Linda Kasaova1, Jakub Grepl1, Petr Motycka2, Ahmed Asqar2, Petr Paluska1, Vladimır Ninger3, Ivana Bydzovska3, Viliam Kopecky3, Jirı Petera1 1
Department of Oncology and Radiotherapy, University Hospital and Medical Faculty, Hradec Kralove, Czech Republic 2 Department of Surgery, University Hospital, Hradec Kralove, Czech Republic 3 Department of Surgery, Hospital Chrudim, Chrudim, Czech Republic
ABSTRACT
PURPOSE: To assess the feasibility of high-dose-rate perioperative multicatheter interstitial brachytherapy to deliver accelerated partial breast irradiation (APBI) in selected patients with early breast cancer. METHODS AND MATERIALS: Perioperative multicatheter interstitial brachytherapy for APBI has been used at our department since 2012 for patients with low-risk breast cancer. Interstitial catheters were inserted perioperatively via hollow needles immediately following tumorectomy with sentinel node biopsy. APBI started on Day 6 after surgery. The prescribed dose was 34 Gy (10 fractions of 3.4 Gy bid). Hormonal therapy was prescribed in all cases. RESULTS: Between June 2012 and December 2017, 125 patients were scheduled for APBI. Of these, APBI was not performed in 12 patients (9.6%) due to adverse prognostic factors identified on the definitive biopsy. We observed wound dehiscence in 2/113 cases (1.8%), inflammatory complications requiring antibiotics in 7/113 cases (6.2%), transient Grade I radiodermatitis in 6/113 patients (4.4%), and seroma which resolved spontaneously in 3/113 patients (2.7%). With median followup of 39 months (range 3.3e75.3) no relapses were observed. No late complications in Radiation Therapy Oncology Group Grade 3 or higher were documented. Cosmetic outcome in patients with followup O 2 years was excellent or good in 92%. CONCLUSION: Our preliminary results show that the perioperative multicatheter interstitial high-dose-rate brachytherapy for APBI in selected patients with early breast cancer is feasible. This treatment schedule reduces treatment duration, spares the patients of repeated anesthesia, and enables precise application of the afterloading tubes under direct visual control. Ó 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Keywords:
Breast cancer; Brachytherapy; APBI; Perioperative
Introduction Breast-conserving surgery (BCS) with adjuvant whole breast irradiation (WBI) with or without additional boost irradiation to the tumor bed has become the standard treatment of early-stage breast carcinoma. The use of WBI
Received 25 July 2018; received in revised form 14 August 2018; accepted 15 August 2018. Financial disclosure: Authors declare no financial disclosure. Conflicts of interest: The authors declare no conflict of interest. * Corresponding author. Department of Oncology and Radiotherapy, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic. Tel.: þ00420-495-832-176; fax: þ00420-495832-081. E-mail address: [email protected] (I. Sirak).
following BCS significantly decreases 10-year locoregional recurrence rates in all patients and 15-year mortality in some of them (1). Despite the undoubted advantages of WBI in terms of improved survival and relapse rates, this approach presents several important drawbacks. First, WBI requires an extended treatment time (3e7 weeks), which places a heavy burden on patients and also increases staff workloads. Second, WBI may be overtreatment given that the vast majority of local relapses (85% or more) that occur after BCS (with or without WBI) occur in or close to the primary tumor bed (2). As a result, irradiating the entire breast needlessly puts patients at risk of developing clinically significant side effects. For these reasons, accelerated partial breast irradiation (APBI), which targets only the tumor
1538-4721/$ - see front matter Ó 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.brachy.2018.08.012
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bed, has been proposed as an alternative to WBI. Several Phases II and III (3e6) clinical studies have been conducted in patients with early-stage breast cancer and a very low risk of local recurrence. APBI has two primary advantages over WBI: fewer radiation-related side effects due to the more precisely targeted dose delivery, and a shorter total treatment time. Various APBI techniques are available, including interstitial multicatheter brachytherapy (MIB), industrial brachytherapy catheters (MammoSite or Contura Balloon applicator, ClearPath or SAVI implants), intraoperative external beam radiotherapy (IORT), and high-precision external beam radiotherapy (EBRT). A systematic review with meta-analysis of 8653 women treated by APBI in eight randomized trials found that patients treated with APBI had a higher rate of local recurrence versus WBI but without any differences in other clinical outcomes (7). Several medical societiesdnotably the American Society of Radiation Oncology (ASTRO), the Groupe Europeen de Curietherapie - European Society for Therapeutic Radiology and Oncology (GEC-ESTRO), and the American Brachytherapy Society (ABS)dhave provided recommendations aimed at reducing the risk of local recurrence in patients who undergo APBI (8e10). Longeterm outcomes for APBI are well documented for MIB but less for other APBI techniques (3, 4). In the studies carried out to date, MIB was performed several weeks after BCS to assure complete wound healing and availability of the full pathological report. However, at our institution, we decided to perform MIB perioperatively based on our previous experience with perioperative brachytherapy in soft tissue sarcomas (11). The aim of our approach is to further reduce treatment duration, thus sparing patients the burden and risks of repeated anesthesia, while enabling the most precise application of the afterloading tubes into the whole cavity under direct visual control during surgery. Here, we describe the perioperative high-dose-rate (HDR) MIB procedure, impact of definitive histopathological finding on the APBI feasibility in a group of selected patients treated for early-stage breast cancer, surgical complications in radiation toxicity, and early cosmetic outcome.
Methods and materials From June 2012 to December 2017, 125 patients were scheduled to receive APBI delivered by perioperative MIB at our department. Inclusion criteria were age $55 years; diagnosis of invasive ductal/lobular carcinoma or ductal carcinoma in situ # 3 cm pN0M0; unifocal and unicentric disease; clear resection margin (‘‘no tumor in ink’’) (10), hormone sensitive; any grade tumors were eligible provided that no nodal or blood vessel invasion was present; HER 2 and BRCA negative. The pretreatment evaluations included mammography, breast ultrasound,
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core cut biopsy, thoracic X-ray, liver ultrasound, and preoperative medical analytical evaluation. All patients were required to provide written informed consent before treatment. The study was approved by the institutional ethical committee. Patient and tumor characteristics are shown in Table 1. Surgery and brachytherapy Tumorectomy with a macroscopic safety margin of 1 cm and sentinel lymph node biopsy were performed. Four titanium clips were inserted in cranial, caudal, medial, and lateral directions to mark the tumor bed. A drain was placed in the excision cavity to decrease postoperative seroma. Stainless hollow steel needles were inserted into the whole surgical cavity while maintaining a distance of $5 mm from the underlying ribs and 10 mm from the skin surface. The needles were applied with 15 mm spacing in a triangular setting in one to four planes. The implant planes were inserted according to the tumor location (deep, middle, superficial) and presumed clinical treatment volume (CTV) shape (pyramid, ovoid, cylindrical), to cover the edge of the CTV. The guide needles were replaced with plastic catheters afterward and secured with fixation buttons, after which the wound was sutured. Until September 2014, we used a freehand technique (first 47 patients; subsequent to that date, we implemented a custom-designed template to improve implant geometry (Fig. 1). The patients were transferred to the Radiotherapy Department 4e5 days after surgery. The surgical drain was removed immediately before planning CT. The CT slices were obtained in 1 mm distances. The 3D positions of afterloading catheters, Table 1 Patients and tumor characteristics Characteristic
n (range)
Median followup (months) Median age (years) Mean tumor diameter (mm) Grading (%) G1 G2 G3 Mean Ki 67 Localization Right Left Upper outer Upper inner Lower outer Lower inner Central Mean surgical margin (mm) Histological subtype (%) Invasive ductal Invasive lobular DCIS Antihormonal treatment
39 18 SD (3.3e72.3) 67 5.8 SD (54e83) 10.0 4.9 SD (2.0e35.0)
DCIS 5 ductal carcinoma in situ.
58 61 6 15.0 8.6 SD (2e60) 57 68 72 24 7 11 11 3.4 3.1 SD (0.1e15.0) 113 8 4 118
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Fig. 1. Perioperative implant technique using custom-designed template to improve geometry.
surgical clips, and skin were reconstructed. The anticipated position of the original tumor was delineated to account for the surgical breast scar, surgical clips, and preoperative mammography (anticipated tumor bed volume [ATBV]). The skin volume was defined 5 mm beyond the body surface. The CTV was defined to ensure safety margins of $20 mm in all directions around the ATBV, incorporating surgical safety margins reconstructed in six directions. The prescribed dose to the CTV was 34 Gy in 10 fractions delivered twice daily (minimal tumor dose [MTD]). Coverage requirements were as follows: 90% of CTV covered by $90% of the MTD; skin Dmax # MTD. To assess implant quality, we calculated cumulative dosevolume histograms and used the dose nonuniformity ratio ([DNR], V150/V100). The plan calculation was performed on the BrachyVision planning system (Varian Medical Systems; Palo Alto, CA). Treatments were delivered using GammaMed Plus HDR afterloading system (MDS Nordion, Haan, Germany) on the sixth day after surgery. We did not use antibiotics for infection prophylaxis, only for local disinfection of the catheter insertion and removal sites. After delivery of the final brachytherapy fraction, the afterloading tubes were removed and patients were discharged. Adjuvant hormonal therapy (anastrozole or tamoxifen) was indicated in all patients. Followup examinations were scheduled 1 and 2 months after brachytherapy and then every 3 months for the first 5 years after radiotherapy, whereas hormonal treatment was ongoing and later in 1 year intervals. The first postoperative mammography and ultrasound were performed 6 months after completion of brachytherapy and yearly thereafter. The acute toxicity was scored according to Common Terminology Criteria for Adverse Event v 4.0 ([CTCAE]: publish date: May 28, 2009). In patients with minimum of 2-year followup, the late toxicity was scored according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC)
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(12), and the cosmetic outcome was evaluated with standardized cosmetic rating scale excellent (Fig. 2)egoodefair (Fig. 3)epoor (13). Photographic documentation of all patients was obtained. In addition, breast symmetry, hyperpigmentation, catheter puncture marks, skin teleangiextasia, and skin-subcutaneous atrophy of fibrosis were classified excellent (0 point), good (1 point), fair (2 points), and poor (3 points) according to system used by Cambeiro et al. (14). Basic descriptive statistics were adopted for the analysis: median, mean, and standard deviations for continuous data, and absolute and relative frequencies for categorical data. The Wilcoxon Rank-Sum Test for difference in medians was used to assess the difference between DNR in patients with freehand application and template. We considered p ! 0.05 to be statistically significant. All statistical analyses were performed using the NCSS 8 statistical software program (NCSS, Keysville, Utah). Results From June 2012 until December 2017, 125 patients were referred for perioperative APBI with MIB at our department. Of these, 12 patients (9.6%) did not receive APBI as monotherapy due to the presence of adverse prognostic factors on the definitive biopsy as follows: lymphangioinvasion in 3 patients; metastatic involvement detected on the sentinel node biopsy in 4 patients; multifocal tumor in 4 patients; intrammarian positive lymphatic node in 1 patient. In those 12 patients, the brachytherapy implant was used as a boost (4 3.0 Gy bid) for the subsequent external beam irradiation. APBI was delivered as planned in 113 of the original 125 patients (90.4%). The implant characteristics are presented in Table 2. The change from the freehand technique to template navigation was associated with significant improvement of the DNR (mean 0.35 in the first 47 patients with freehand technique and mean 0.22 in the 66 patients with the template, p ! 0.00001, Fig. 4). The entire course
Fig. 2. Example of excellent cosmetic outcome.
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Fig. 3. Example of fair cosmetic outcome.
of radiotherapy was completed in 6 days, including 1 day for planning. All patients were discharged from the hospital between 12 and 14 days following surgery. We observed delayed healing due to wound dehiscence in 2/113 cases (1.8%), inflammatory complications requiring antibiotics in 7/113 cases (6.2%), transient Grade I radiodermatitis in 6/113 patients (4.4%), and seroma which resolved spontaneously in 3/113 patients (2.7%). Table 3 shows late radiation effects occurring O3 month after radiotherapy and Table 4 cosmetic outcome in 89 patients with followup O 24 month. Three patients suffered by breast pain visual analog scale for pain 1, and 1 patient had persistent seroma not indicated for evacuation. We have not documented any case of fat necrosis yet. Up to now no recurrences have been observed.
Discussion MIB is a well-established technique for APBI (15). However, it is generally performed several weeks after surgery to avoid possible wound healing complications and only after complete results of the pathological examination Table 2 Characteristics of the brachytherapy applications Characteristic
n (range), SD 5 standard deviation
Median number of catheters Median number of planes Mean V100 (cm3) Mean V150 (cm3) Mean skin dose (Gy) Mean DNR all 113 patients Mean DNR without template (47 patients) Mean DNR with template (66 patients)
13 3 SD 31 51.5 29.6 SD 12.7 12.6 SD 29.0 6.6 SD 0.23 0.11 SD 0.35 0.14 SD
DNR 5 dose nonuniformity ratio.
(4; 19) (1e4) (9.9e153.6) (2.5e67.2) (9e45) (0.15e0.57) (0.15e0.57)
0.21 0.04 SD (0.15e0.34)
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are available. We conducted this study to evaluate the feasibility of using perioperative MIB (starting 6 days postoperatively) in highly selected patients with early breast cancer with respect to impact of final histopathological finding. In this setting, the appropriateness of APBI, surgical, infectious, early radiation complications and late complications, and cosmetic outcome in patients with minimal followup at least 24 months is reported. Perioperative MIB is frequently used to deliver a boost to the tumor bed in combination with WBI (16). In the targeted IORT (TARGIT) study, of the 1140 patients allocated to TARGIT in the prepathology stratum, 219 (19%) ultimately received both IORT and WBI because postoperative evaluation revealed high-risk characteristics in that subset of patients (5). Similarly, in a study of patients treated with MammoSite brachytherapy, 17 of 43 patients (39.5%) were disqualified from APBI based on histologic findings (17). In another study, Aristei et al. (18) inserted implants during surgery in 15 of 65 cases, with subsequent histological findings precluding APBI in 4 patients (27%), requiring either implant removal or repurposing as a boost. The authors of that study concluded that the main advantages of intraoperative implantation are that it allows the radiation oncologist to visualize the surgical cavity and also allows for a rapid completion of both surgery and radiotherapy (7e10 days), a conclusion with which we agree. In the recent study, Cambeiro et al. (14) with perioperative MIP in early breast cancer, the APBI was performed in 88 from 137 initial candidates (64.2%); in 34 patients (24.8%), the implant was used as the boost to EBRT; and brachytherapy was not performed in 15 cases (11%). The reasons for cancellation of APBI were positive sentinel nodes, small breast unsuitable for implant after BCS, multicentric tumor, fear of complication in oncoplastic surgery, positive margins, bleeding, and unfulfilled dosimetry targets. In our study, the planned APBI procedures were performed in 90.4% of patients. In the remaining patients with inadequate pathological features, we were able to successfully repurpose the implant as a boost for the WBI. The low rate of failure to realize APBI monotherapy in our study may be related to the relatively strict inclusion criteria used in our study, and a higher tolerance to nonoptimal dosimetry parameters in our first patients, in contrast to Cambeiro study. Nevertheless, based on the low rate of adverse histological findings in our carefully selected population, APBI with MIB seems to be a reasonable approach. The question can be whether radiotherapy makes sense in women $60 years of age with early luminal A tumors. According to the German Society for Radiation Oncology practical guidelines for breast cancer, no subgroup (not even elderly patients) has been identified that would not benefit from radiotherapy in terms of local control (19). We observed delayed wound dehiscence in 1.8%, infection in 6.2%, seroma in 2.7%, and transient Grade I radiodermatitis in 4.4% patients. This low incidence of acute complications is in agreement with previously published
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Fig. 4. Learning curve demonstrating the improvement of the DHI (Dose Homogeneity Index; 1eDNR) with increasing number of patients in time.
results. In two recent studies (Dolezel et al. (20) and Sharma et al. (16)) in which perioperative brachytherapy was used as a boost, wound complications were described in Table 3 Late radiation consequences RTOG/EORTC skin Grade 0 Grade 1 Grade 2 Grade 3 RTOG/EORTC subcutaneous tissue Grade 0 Grade 1 Grade 2 Grade 3 Symmetry Symmetry Acceptable difference Obvious difference Marked difference Hyperpigmentation Nonvisible Slightly visible Obvious Marked Catheter puncture marks Not visible Slightly visible Obvious Marked Skin telangiectasia Not visible Slightly visible Obvious Marked
69/113 (61.0%) 36/113 (31.9%) 8/113 (7.1%) 0 88/113 (77.9%) 20/113 (17.7%) 5/113 (4.4%) 0 94/113 (83.2%) 10/113 (8.8%) 9/113 (8.0%) 0 109/113 (96.4%) 4/113 (3.6%) 0 0 88/113 (77.8%) 24/113 (21.2%) 1/113 (1%) 0 102/113 (90.4%) 8/113 (7%) 3/113 (2.6%) 0
RTOG/EORTC 5 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer.
4% of patients, and acute Grade I skin toxicity in 7% (20) and 13% (16) and of cases, respectively. In the German-Austrian Phase II trial, Strnad et al. (21) with postoperative MIB for APBI, Grade 1e2 radiodermatitis, bacterial implant infection, and hematoma were observed in 6.6%, 3.3%, and 2.3% of patients, respectively. The same authors’ team reported Grade I radiodermatitis in 19% and Grade II radiodermatitis in 2% of 663 patients treated by MIB for APBI (22). Evaluation of late toxicity and disease control is limited by short followup. In our study, no tumor recurrence has been observed up to now. The preliminary late radiation consequences are comparable with other studies (14, 23). It could be expected that particularly occurrence of teleangiectasia, fibrosis, and fat necrosis will be higher with longer followup (23), particularly for those patients with a suboptimal DNR. The cosmetic result was scored in 89 patients with followup O 2 years according Wazer et al. (13). Excellent to good result was achieved in 92% according to physician and nurse evaluation and 99% according to the patient, which is in accordance with published studies (14, 23). The cosmetic score does not change with longer followup (23). Unfortunately, we have no photodocumentation after surgery before starting the radiotherapy. Table 4 Cosmetic outcome in 89 patients with followup O 24 month Cosmetic outcome
Physician
Nurse
Patient
Excellent Good Fair Poor
63/89 (71%) 19/89 (21%) 7/89 (8%) 0
58/89 (65%) 24/89 (27%) 7/89 (8%) 0
65/89 (73%) 23/89 (26%) 1/89 (1%) 0
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In our study, the MTD was expressed as the 100% isodose, following the example of the Hungarian study (3). The implant dosimetry in our study is comparable with the most important published results of postoperative MIB APBI (3, 21). The mean volume of the prescribed dose in our study (51.4 cm3) was comparable to the volumes reported in the Hungarian (Polgar et al.) and GermanAustrian studies (50 and 64 cm3, respectively). Similarly, the mean DNR in our study, 0.23 (0.15; 0.57), was similar to the Polgar et al. study (3), that is, 0.45 (0.25; 0.57) but worse than in the Strnad et al. study (21), that is, 0.21 (0.15; 0.39). The DNR improved over time in our study with increasing experience, particularly when we began to use the custom-designed template for implant geometry, that is, to 0.21 (0.15; 0.34). Contrary to our first implants, we currently do not accept DNR O0.30. Interestingly, the DNR with freehand perioperative brachytherapy in the study by Cambeiro et al. (14) was excellent without template, that is, 0.25 (0.16e0.4). The mean V150 5 12.9 cm3 in our study is comparable with Polgar et al. (24 cm3) but higher than that reported by Strnad et al. (9 cm3) (21) and Cambeiro (14) (12.8 cm3). Although the skin dose should be # 100% of the prescribed dose according ASTRO consensus guidelines (8), in 9 of our patients, the skin dose was O100% of the prescribed dose. Importantly, 6 of these patients subsequently developed acute skin erythema. We tried to avoid any changes in techniques based on these findings, as is the modification of the CTV, or acceptance of lower target coverage of 90%. Hormonal treatment was prescribed in all our patients. This strategy could be questioned due to very early stages of the disease, but recent experience supports the use of hormonal treatment in patients with hormoneesensitive breast cancer treated by APBI because of improvements in local control (22, 24). Although the criteria to indicate APBI are strict, the number of suitable patients is growing quickly as a result of the increasing use of screening mammography and population aging. The crude incidence of T1N0M0 breast tumor in the Czech Republic increased from 1266 cases in the year 2000 to 3096 cases in 2012, and 60% of patients are $60 years of age (25). After publication of Polgar study (3) and Strnad study (4), the APBI with MIB became a new standard of adjuvant radiotherapy of early stages of breast cancer. The results of MIB for APBI are better in comparison with balloon brachytherapy, IORT, or EBRT (23). We performed our study with the aim to test the feasibility of perioperative MIB, to reduce the overall time of adjuvant radiotherapy, and to improve their precision. Our results support the hypothesis that perioperative MIB is feasible with good results in selected patients. We started our study before publication of the new ASTRO and American Brachytherapy Society recommendations for APBI. After evaluation of our results, we are prepared to broaden our criteria for perioperative MIB.
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Conclusions Perioperative HDR MIB for APBI in selected patients with early breast carcinoma is feasible. This treatment schedule substantially reduces treatment duration, spares the need for repeated anesthesia with the attendant risk, and enables precise application of the afterloading tubes under direct visual control.
Acknowledgments The study was supported by programme PRVOUK P37/ 06. The funding body had no role in design, collection, analysis or interpretation of the data, writing of the article or the decision to submit the article for publication. We thank Bradley Londres for helping to improve the English in this article. References [1] Early Breast Cancer Trialists Collaborative Group (EBCTCG) Darby S, McGale P, Correa C, et al. Effect of radiotherapy after breast conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data for 10,801 women in 174 randomized trials. Lancet 2011;378:1707e1716. [2] Orecchia R, Fossati P. Partial breast irradiation: Ready for routine? Breast 2007;16:89e97. [3] Polgar C, Major T, Fodor J, et al. Accelerated partial-breast irradiation using high-dose-rate interstitial brachytherapy: 12-year update of a prospective clinical study. Radiother Oncol 2010;94:274e279. [4] Strnad V, Ott OJ, Hildebrandt G, et al. 5-year result of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast e conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: A randomised, phase 3, non-inferiority trial. Lancet 2016;387:229e238. [5] Valdya JS, Wenz F, Bulsara M, et al. Risk adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGITA randomized trial. Lancet 2014;383:603e613. [6] Veronesi U, Orecchia R, Maisonneuve P, et al. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): A randomised controlled equivalence trial. Lancet Oncol 2013;14: 1269e1277. [7] Marta GN, Macedo CR, Carvalho HA, et al. Accelerated partial irradiation for breast cancer: Systematic review and meta-analysis of 8653 women in eight randomized trials. Radiother Oncol 2015;14: 42e49. [8] Smith BD, Arthur DW, Buchholz TA, et al. Accelerated partial breast irradiation consensus statement from the American society for radiation oncology (ASTRO). Int J Radiat Oncol Biol Phys 2009;74:987e 1001. [9] Polgar C, Van Limbergen W, P€otter R, et al. Patient selection for accelerated partial breast irradiation (APBI) after breast conserving surgery: Recommendations of the Groupe Europeen de Curietherapie- European society for therapeutic radiology and oncology (GEC-ESTRO) breast cancer working group. Radiother Oncol 2010;94:234e273. [10] Shah C, Vicini F, Wazer DE, et al. The American Brachytherapy Society consensus statement for accelerated partial breast irradiation. Brachytherapy 2013;12:267e277. [11] Petera J, Soumarova R, R uzickova J, et al. Perioperative hyperfractionated high-dose rate brachytherapy for the treatment of soft
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[12]
[13]
[14]
[15]
[16]
[17]
[18]
tissue sarcomas: Multicentric experience. Ann Surg Oncol 2010;17: 206e210. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys 1995;31:1341e1346. Wazer DE, Kaufman S, Cuttino L, et al. Accelerated partial breast irradiation: An analysis of variables associated with late toxicity and long-term cosmetic outcome after high-dose-rate interstitial brachytherapy. Int J Radiat Oncol Biol Phys 2006;64:489e495. Cambeiro M, Martinez-Regueira F, Rodriguez-Spiteri N, et al. Multicatheter breast implant during breast conservative surgery: Novel approach to deliver accelerated partial breast irradiation. Brachytherapy 2016;15:458e494. Murawa P, Murawa D, Adamczyk B, et al. Breast cancer: Actual methods of treatment and future trends. Rep Pract Oncol Radiother 2014;19:165e172. Sharma DN, Deo SVS, Rath GK, et al. Perioperative high-dose rate interstitial boost for patients with early breast cancer. Tumori 2013; 99:604e610. Belkacemi Y, Chauver MP, Giard S, et al. Partial breast irradiation as sole therapy for low risk breast carcinoma: early toxicity, cosmesis and quality of life results of a MammoSite brachytherapy. Radiother Oncol 2009;90:23e29. Aristei C, Palumbo I, Cucciarelli F, et al. Partial breast irradiation with interstitial high-dose - rate brachytherapy in early breast cancer: Results of a phase II prospective study. Eur J Surg Oncol 2009;35: 144e150.
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[19] Sedlmayer F, SauttereBihl ML, Budach W, et al. DFEGRO practical guidelines : Radiotherapy of breast cancer I. Strahlenther Onkol 2013;10:825e833. [20] Dolezel M, Stastny K, Odrazka K, et al. Perioperative interstitial CTbased brachytherapy boost in breast cancer opatients with breast conservation after neoadjuvant chemotherapy. Neoplasma 2012;59:494e499. [21] Strnad V, Hildebrandt G, P€otter R, et al. Accelerated partial breast irradiation: 5eyear results of the German-Austrian multicentre phase II trial using interstitial multicatheter brachytherapy alone after breast-conserving surgery. Int J Radiat Oncol Biol Phys 2011;80: 17e24. [22] Ott OJ, Strnad V, Hildebrandt G, et al. GEC-ESTRO multicentre phase 3-trial: Accelerated partial breast irradiation with interstitial multicatheter brachytherapy versus external beam whole breast irradiation: Early toxicity and patients compliance. Radiother Oncol 2016;120:119e123. [23] Polgar C, Hildebrand G, Kauer Dorner D, et al. Late side-effects and cosmetic result of accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation after breastconserving surgery for low.risk invasive and in-situ carcinoma of the female breast: 5-year results of a randomized, controlled, phase 3 trial. Lancet Oncol 2017;18:259e268. [24] Antonucci JV, Wallace M, Goldstein NS, et al. Differences in patterns of failure in patients treated with accelerated partial breast irradiation versus whole-breast irradiation: A matched-pair analysis with 10 year follow-up. Int J Radiat Oncol Biol Phys 2009;74:447e452. [25] Cancer incidence in the czech republic. Prague, Czech Republic: 2015. UZIS CR;
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Accelerated partial breast irradiation with perioperative multicatheter interstitial brachytherapydA feasibility study Denisa Pohankova1, Igor Sirak1,*, Pavel Jandık2, Linda Kasaova1, Jakub Grepl1, Petr Motycka2, Ahmed Asqar2, Petr Paluska1, Vladimır Ninger3, Ivana Bydzovska3, Viliam Kopecky3, Jirı Petera1 1
Department of Oncology and Radiotherapy, University Hospital and Medical Faculty, Hradec Kralove, Czech Republic 2 Department of Surgery, University Hospital, Hradec Kralove, Czech Republic 3 Department of Surgery, Hospital Chrudim, Chrudim, Czech Republic
ABSTRACT
PURPOSE: To assess the feasibility of high-dose-rate perioperative multicatheter interstitial brachytherapy to deliver accelerated partial breast irradiation (APBI) in selected patients with early breast cancer. METHODS AND MATERIALS: Perioperative multicatheter interstitial brachytherapy for APBI has been used at our department since 2012 for patients with low-risk breast cancer. Interstitial catheters were inserted perioperatively via hollow needles immediately following tumorectomy with sentinel node biopsy. APBI started on Day 6 after surgery. The prescribed dose was 34 Gy (10 fractions of 3.4 Gy bid). Hormonal therapy was prescribed in all cases. RESULTS: Between June 2012 and December 2017, 125 patients were scheduled for APBI. Of these, APBI was not performed in 12 patients (9.6%) due to adverse prognostic factors identified on the definitive biopsy. We observed wound dehiscence in 2/113 cases (1.8%), inflammatory complications requiring antibiotics in 7/113 cases (6.2%), transient Grade I radiodermatitis in 6/113 patients (4.4%), and seroma which resolved spontaneously in 3/113 patients (2.7%). With median followup of 39 months (range 3.3e75.3) no relapses were observed. No late complications in Radiation Therapy Oncology Group Grade 3 or higher were documented. Cosmetic outcome in patients with followup O 2 years was excellent or good in 92%. CONCLUSION: Our preliminary results show that the perioperative multicatheter interstitial high-dose-rate brachytherapy for APBI in selected patients with early breast cancer is feasible. This treatment schedule reduces treatment duration, spares the patients of repeated anesthesia, and enables precise application of the afterloading tubes under direct visual control. Ó 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Keywords:
Breast cancer; Brachytherapy; APBI; Perioperative
Introduction Breast-conserving surgery (BCS) with adjuvant whole breast irradiation (WBI) with or without additional boost irradiation to the tumor bed has become the standard treatment of early-stage breast carcinoma. The use of WBI
Received 25 July 2018; received in revised form 14 August 2018; accepted 15 August 2018. Financial disclosure: Authors declare no financial disclosure. Conflicts of interest: The authors declare no conflict of interest. * Corresponding author. Department of Oncology and Radiotherapy, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic. Tel.: þ00420-495-832-176; fax: þ00420-495832-081. E-mail address: [email protected] (I. Sirak).
following BCS significantly decreases 10-year locoregional recurrence rates in all patients and 15-year mortality in some of them (1). Despite the undoubted advantages of WBI in terms of improved survival and relapse rates, this approach presents several important drawbacks. First, WBI requires an extended treatment time (3e7 weeks), which places a heavy burden on patients and also increases staff workloads. Second, WBI may be overtreatment given that the vast majority of local relapses (85% or more) that occur after BCS (with or without WBI) occur in or close to the primary tumor bed (2). As a result, irradiating the entire breast needlessly puts patients at risk of developing clinically significant side effects. For these reasons, accelerated partial breast irradiation (APBI), which targets only the tumor
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bed, has been proposed as an alternative to WBI. Several Phases II and III (3e6) clinical studies have been conducted in patients with early-stage breast cancer and a very low risk of local recurrence. APBI has two primary advantages over WBI: fewer radiation-related side effects due to the more precisely targeted dose delivery, and a shorter total treatment time. Various APBI techniques are available, including interstitial multicatheter brachytherapy (MIB), industrial brachytherapy catheters (MammoSite or Contura Balloon applicator, ClearPath or SAVI implants), intraoperative external beam radiotherapy (IORT), and high-precision external beam radiotherapy (EBRT). A systematic review with meta-analysis of 8653 women treated by APBI in eight randomized trials found that patients treated with APBI had a higher rate of local recurrence versus WBI but without any differences in other clinical outcomes (7). Several medical societiesdnotably the American Society of Radiation Oncology (ASTRO), the Groupe Europeen de Curietherapie - European Society for Therapeutic Radiology and Oncology (GEC-ESTRO), and the American Brachytherapy Society (ABS)dhave provided recommendations aimed at reducing the risk of local recurrence in patients who undergo APBI (8e10). Longeterm outcomes for APBI are well documented for MIB but less for other APBI techniques (3, 4). In the studies carried out to date, MIB was performed several weeks after BCS to assure complete wound healing and availability of the full pathological report. However, at our institution, we decided to perform MIB perioperatively based on our previous experience with perioperative brachytherapy in soft tissue sarcomas (11). The aim of our approach is to further reduce treatment duration, thus sparing patients the burden and risks of repeated anesthesia, while enabling the most precise application of the afterloading tubes into the whole cavity under direct visual control during surgery. Here, we describe the perioperative high-dose-rate (HDR) MIB procedure, impact of definitive histopathological finding on the APBI feasibility in a group of selected patients treated for early-stage breast cancer, surgical complications in radiation toxicity, and early cosmetic outcome.
Methods and materials From June 2012 to December 2017, 125 patients were scheduled to receive APBI delivered by perioperative MIB at our department. Inclusion criteria were age $55 years; diagnosis of invasive ductal/lobular carcinoma or ductal carcinoma in situ # 3 cm pN0M0; unifocal and unicentric disease; clear resection margin (‘‘no tumor in ink’’) (10), hormone sensitive; any grade tumors were eligible provided that no nodal or blood vessel invasion was present; HER 2 and BRCA negative. The pretreatment evaluations included mammography, breast ultrasound,
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core cut biopsy, thoracic X-ray, liver ultrasound, and preoperative medical analytical evaluation. All patients were required to provide written informed consent before treatment. The study was approved by the institutional ethical committee. Patient and tumor characteristics are shown in Table 1. Surgery and brachytherapy Tumorectomy with a macroscopic safety margin of 1 cm and sentinel lymph node biopsy were performed. Four titanium clips were inserted in cranial, caudal, medial, and lateral directions to mark the tumor bed. A drain was placed in the excision cavity to decrease postoperative seroma. Stainless hollow steel needles were inserted into the whole surgical cavity while maintaining a distance of $5 mm from the underlying ribs and 10 mm from the skin surface. The needles were applied with 15 mm spacing in a triangular setting in one to four planes. The implant planes were inserted according to the tumor location (deep, middle, superficial) and presumed clinical treatment volume (CTV) shape (pyramid, ovoid, cylindrical), to cover the edge of the CTV. The guide needles were replaced with plastic catheters afterward and secured with fixation buttons, after which the wound was sutured. Until September 2014, we used a freehand technique (first 47 patients; subsequent to that date, we implemented a custom-designed template to improve implant geometry (Fig. 1). The patients were transferred to the Radiotherapy Department 4e5 days after surgery. The surgical drain was removed immediately before planning CT. The CT slices were obtained in 1 mm distances. The 3D positions of afterloading catheters, Table 1 Patients and tumor characteristics Characteristic
n (range)
Median followup (months) Median age (years) Mean tumor diameter (mm) Grading (%) G1 G2 G3 Mean Ki 67 Localization Right Left Upper outer Upper inner Lower outer Lower inner Central Mean surgical margin (mm) Histological subtype (%) Invasive ductal Invasive lobular DCIS Antihormonal treatment
39 18 SD (3.3e72.3) 67 5.8 SD (54e83) 10.0 4.9 SD (2.0e35.0)
DCIS 5 ductal carcinoma in situ.
58 61 6 15.0 8.6 SD (2e60) 57 68 72 24 7 11 11 3.4 3.1 SD (0.1e15.0) 113 8 4 118
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Fig. 1. Perioperative implant technique using custom-designed template to improve geometry.
surgical clips, and skin were reconstructed. The anticipated position of the original tumor was delineated to account for the surgical breast scar, surgical clips, and preoperative mammography (anticipated tumor bed volume [ATBV]). The skin volume was defined 5 mm beyond the body surface. The CTV was defined to ensure safety margins of $20 mm in all directions around the ATBV, incorporating surgical safety margins reconstructed in six directions. The prescribed dose to the CTV was 34 Gy in 10 fractions delivered twice daily (minimal tumor dose [MTD]). Coverage requirements were as follows: 90% of CTV covered by $90% of the MTD; skin Dmax # MTD. To assess implant quality, we calculated cumulative dosevolume histograms and used the dose nonuniformity ratio ([DNR], V150/V100). The plan calculation was performed on the BrachyVision planning system (Varian Medical Systems; Palo Alto, CA). Treatments were delivered using GammaMed Plus HDR afterloading system (MDS Nordion, Haan, Germany) on the sixth day after surgery. We did not use antibiotics for infection prophylaxis, only for local disinfection of the catheter insertion and removal sites. After delivery of the final brachytherapy fraction, the afterloading tubes were removed and patients were discharged. Adjuvant hormonal therapy (anastrozole or tamoxifen) was indicated in all patients. Followup examinations were scheduled 1 and 2 months after brachytherapy and then every 3 months for the first 5 years after radiotherapy, whereas hormonal treatment was ongoing and later in 1 year intervals. The first postoperative mammography and ultrasound were performed 6 months after completion of brachytherapy and yearly thereafter. The acute toxicity was scored according to Common Terminology Criteria for Adverse Event v 4.0 ([CTCAE]: publish date: May 28, 2009). In patients with minimum of 2-year followup, the late toxicity was scored according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC)
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(12), and the cosmetic outcome was evaluated with standardized cosmetic rating scale excellent (Fig. 2)egoodefair (Fig. 3)epoor (13). Photographic documentation of all patients was obtained. In addition, breast symmetry, hyperpigmentation, catheter puncture marks, skin teleangiextasia, and skin-subcutaneous atrophy of fibrosis were classified excellent (0 point), good (1 point), fair (2 points), and poor (3 points) according to system used by Cambeiro et al. (14). Basic descriptive statistics were adopted for the analysis: median, mean, and standard deviations for continuous data, and absolute and relative frequencies for categorical data. The Wilcoxon Rank-Sum Test for difference in medians was used to assess the difference between DNR in patients with freehand application and template. We considered p ! 0.05 to be statistically significant. All statistical analyses were performed using the NCSS 8 statistical software program (NCSS, Keysville, Utah). Results From June 2012 until December 2017, 125 patients were referred for perioperative APBI with MIB at our department. Of these, 12 patients (9.6%) did not receive APBI as monotherapy due to the presence of adverse prognostic factors on the definitive biopsy as follows: lymphangioinvasion in 3 patients; metastatic involvement detected on the sentinel node biopsy in 4 patients; multifocal tumor in 4 patients; intrammarian positive lymphatic node in 1 patient. In those 12 patients, the brachytherapy implant was used as a boost (4 3.0 Gy bid) for the subsequent external beam irradiation. APBI was delivered as planned in 113 of the original 125 patients (90.4%). The implant characteristics are presented in Table 2. The change from the freehand technique to template navigation was associated with significant improvement of the DNR (mean 0.35 in the first 47 patients with freehand technique and mean 0.22 in the 66 patients with the template, p ! 0.00001, Fig. 4). The entire course
Fig. 2. Example of excellent cosmetic outcome.
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Fig. 3. Example of fair cosmetic outcome.
of radiotherapy was completed in 6 days, including 1 day for planning. All patients were discharged from the hospital between 12 and 14 days following surgery. We observed delayed healing due to wound dehiscence in 2/113 cases (1.8%), inflammatory complications requiring antibiotics in 7/113 cases (6.2%), transient Grade I radiodermatitis in 6/113 patients (4.4%), and seroma which resolved spontaneously in 3/113 patients (2.7%). Table 3 shows late radiation effects occurring O3 month after radiotherapy and Table 4 cosmetic outcome in 89 patients with followup O 24 month. Three patients suffered by breast pain visual analog scale for pain 1, and 1 patient had persistent seroma not indicated for evacuation. We have not documented any case of fat necrosis yet. Up to now no recurrences have been observed.
Discussion MIB is a well-established technique for APBI (15). However, it is generally performed several weeks after surgery to avoid possible wound healing complications and only after complete results of the pathological examination Table 2 Characteristics of the brachytherapy applications Characteristic
n (range), SD 5 standard deviation
Median number of catheters Median number of planes Mean V100 (cm3) Mean V150 (cm3) Mean skin dose (Gy) Mean DNR all 113 patients Mean DNR without template (47 patients) Mean DNR with template (66 patients)
13 3 SD 31 51.5 29.6 SD 12.7 12.6 SD 29.0 6.6 SD 0.23 0.11 SD 0.35 0.14 SD
DNR 5 dose nonuniformity ratio.
(4; 19) (1e4) (9.9e153.6) (2.5e67.2) (9e45) (0.15e0.57) (0.15e0.57)
0.21 0.04 SD (0.15e0.34)
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are available. We conducted this study to evaluate the feasibility of using perioperative MIB (starting 6 days postoperatively) in highly selected patients with early breast cancer with respect to impact of final histopathological finding. In this setting, the appropriateness of APBI, surgical, infectious, early radiation complications and late complications, and cosmetic outcome in patients with minimal followup at least 24 months is reported. Perioperative MIB is frequently used to deliver a boost to the tumor bed in combination with WBI (16). In the targeted IORT (TARGIT) study, of the 1140 patients allocated to TARGIT in the prepathology stratum, 219 (19%) ultimately received both IORT and WBI because postoperative evaluation revealed high-risk characteristics in that subset of patients (5). Similarly, in a study of patients treated with MammoSite brachytherapy, 17 of 43 patients (39.5%) were disqualified from APBI based on histologic findings (17). In another study, Aristei et al. (18) inserted implants during surgery in 15 of 65 cases, with subsequent histological findings precluding APBI in 4 patients (27%), requiring either implant removal or repurposing as a boost. The authors of that study concluded that the main advantages of intraoperative implantation are that it allows the radiation oncologist to visualize the surgical cavity and also allows for a rapid completion of both surgery and radiotherapy (7e10 days), a conclusion with which we agree. In the recent study, Cambeiro et al. (14) with perioperative MIP in early breast cancer, the APBI was performed in 88 from 137 initial candidates (64.2%); in 34 patients (24.8%), the implant was used as the boost to EBRT; and brachytherapy was not performed in 15 cases (11%). The reasons for cancellation of APBI were positive sentinel nodes, small breast unsuitable for implant after BCS, multicentric tumor, fear of complication in oncoplastic surgery, positive margins, bleeding, and unfulfilled dosimetry targets. In our study, the planned APBI procedures were performed in 90.4% of patients. In the remaining patients with inadequate pathological features, we were able to successfully repurpose the implant as a boost for the WBI. The low rate of failure to realize APBI monotherapy in our study may be related to the relatively strict inclusion criteria used in our study, and a higher tolerance to nonoptimal dosimetry parameters in our first patients, in contrast to Cambeiro study. Nevertheless, based on the low rate of adverse histological findings in our carefully selected population, APBI with MIB seems to be a reasonable approach. The question can be whether radiotherapy makes sense in women $60 years of age with early luminal A tumors. According to the German Society for Radiation Oncology practical guidelines for breast cancer, no subgroup (not even elderly patients) has been identified that would not benefit from radiotherapy in terms of local control (19). We observed delayed wound dehiscence in 1.8%, infection in 6.2%, seroma in 2.7%, and transient Grade I radiodermatitis in 4.4% patients. This low incidence of acute complications is in agreement with previously published
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Fig. 4. Learning curve demonstrating the improvement of the DHI (Dose Homogeneity Index; 1eDNR) with increasing number of patients in time.
results. In two recent studies (Dolezel et al. (20) and Sharma et al. (16)) in which perioperative brachytherapy was used as a boost, wound complications were described in Table 3 Late radiation consequences RTOG/EORTC skin Grade 0 Grade 1 Grade 2 Grade 3 RTOG/EORTC subcutaneous tissue Grade 0 Grade 1 Grade 2 Grade 3 Symmetry Symmetry Acceptable difference Obvious difference Marked difference Hyperpigmentation Nonvisible Slightly visible Obvious Marked Catheter puncture marks Not visible Slightly visible Obvious Marked Skin telangiectasia Not visible Slightly visible Obvious Marked
69/113 (61.0%) 36/113 (31.9%) 8/113 (7.1%) 0 88/113 (77.9%) 20/113 (17.7%) 5/113 (4.4%) 0 94/113 (83.2%) 10/113 (8.8%) 9/113 (8.0%) 0 109/113 (96.4%) 4/113 (3.6%) 0 0 88/113 (77.8%) 24/113 (21.2%) 1/113 (1%) 0 102/113 (90.4%) 8/113 (7%) 3/113 (2.6%) 0
RTOG/EORTC 5 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer.
4% of patients, and acute Grade I skin toxicity in 7% (20) and 13% (16) and of cases, respectively. In the German-Austrian Phase II trial, Strnad et al. (21) with postoperative MIB for APBI, Grade 1e2 radiodermatitis, bacterial implant infection, and hematoma were observed in 6.6%, 3.3%, and 2.3% of patients, respectively. The same authors’ team reported Grade I radiodermatitis in 19% and Grade II radiodermatitis in 2% of 663 patients treated by MIB for APBI (22). Evaluation of late toxicity and disease control is limited by short followup. In our study, no tumor recurrence has been observed up to now. The preliminary late radiation consequences are comparable with other studies (14, 23). It could be expected that particularly occurrence of teleangiectasia, fibrosis, and fat necrosis will be higher with longer followup (23), particularly for those patients with a suboptimal DNR. The cosmetic result was scored in 89 patients with followup O 2 years according Wazer et al. (13). Excellent to good result was achieved in 92% according to physician and nurse evaluation and 99% according to the patient, which is in accordance with published studies (14, 23). The cosmetic score does not change with longer followup (23). Unfortunately, we have no photodocumentation after surgery before starting the radiotherapy. Table 4 Cosmetic outcome in 89 patients with followup O 24 month Cosmetic outcome
Physician
Nurse
Patient
Excellent Good Fair Poor
63/89 (71%) 19/89 (21%) 7/89 (8%) 0
58/89 (65%) 24/89 (27%) 7/89 (8%) 0
65/89 (73%) 23/89 (26%) 1/89 (1%) 0
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In our study, the MTD was expressed as the 100% isodose, following the example of the Hungarian study (3). The implant dosimetry in our study is comparable with the most important published results of postoperative MIB APBI (3, 21). The mean volume of the prescribed dose in our study (51.4 cm3) was comparable to the volumes reported in the Hungarian (Polgar et al.) and GermanAustrian studies (50 and 64 cm3, respectively). Similarly, the mean DNR in our study, 0.23 (0.15; 0.57), was similar to the Polgar et al. study (3), that is, 0.45 (0.25; 0.57) but worse than in the Strnad et al. study (21), that is, 0.21 (0.15; 0.39). The DNR improved over time in our study with increasing experience, particularly when we began to use the custom-designed template for implant geometry, that is, to 0.21 (0.15; 0.34). Contrary to our first implants, we currently do not accept DNR O0.30. Interestingly, the DNR with freehand perioperative brachytherapy in the study by Cambeiro et al. (14) was excellent without template, that is, 0.25 (0.16e0.4). The mean V150 5 12.9 cm3 in our study is comparable with Polgar et al. (24 cm3) but higher than that reported by Strnad et al. (9 cm3) (21) and Cambeiro (14) (12.8 cm3). Although the skin dose should be # 100% of the prescribed dose according ASTRO consensus guidelines (8), in 9 of our patients, the skin dose was O100% of the prescribed dose. Importantly, 6 of these patients subsequently developed acute skin erythema. We tried to avoid any changes in techniques based on these findings, as is the modification of the CTV, or acceptance of lower target coverage of 90%. Hormonal treatment was prescribed in all our patients. This strategy could be questioned due to very early stages of the disease, but recent experience supports the use of hormonal treatment in patients with hormoneesensitive breast cancer treated by APBI because of improvements in local control (22, 24). Although the criteria to indicate APBI are strict, the number of suitable patients is growing quickly as a result of the increasing use of screening mammography and population aging. The crude incidence of T1N0M0 breast tumor in the Czech Republic increased from 1266 cases in the year 2000 to 3096 cases in 2012, and 60% of patients are $60 years of age (25). After publication of Polgar study (3) and Strnad study (4), the APBI with MIB became a new standard of adjuvant radiotherapy of early stages of breast cancer. The results of MIB for APBI are better in comparison with balloon brachytherapy, IORT, or EBRT (23). We performed our study with the aim to test the feasibility of perioperative MIB, to reduce the overall time of adjuvant radiotherapy, and to improve their precision. Our results support the hypothesis that perioperative MIB is feasible with good results in selected patients. We started our study before publication of the new ASTRO and American Brachytherapy Society recommendations for APBI. After evaluation of our results, we are prepared to broaden our criteria for perioperative MIB.
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Conclusions Perioperative HDR MIB for APBI in selected patients with early breast carcinoma is feasible. This treatment schedule substantially reduces treatment duration, spares the need for repeated anesthesia with the attendant risk, and enables precise application of the afterloading tubes under direct visual control.
Acknowledgments The study was supported by programme PRVOUK P37/ 06. The funding body had no role in design, collection, analysis or interpretation of the data, writing of the article or the decision to submit the article for publication. We thank Bradley Londres for helping to improve the English in this article. References [1] Early Breast Cancer Trialists Collaborative Group (EBCTCG) Darby S, McGale P, Correa C, et al. Effect of radiotherapy after breast conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data for 10,801 women in 174 randomized trials. Lancet 2011;378:1707e1716. [2] Orecchia R, Fossati P. Partial breast irradiation: Ready for routine? Breast 2007;16:89e97. [3] Polgar C, Major T, Fodor J, et al. Accelerated partial-breast irradiation using high-dose-rate interstitial brachytherapy: 12-year update of a prospective clinical study. Radiother Oncol 2010;94:274e279. [4] Strnad V, Ott OJ, Hildebrandt G, et al. 5-year result of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast e conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: A randomised, phase 3, non-inferiority trial. Lancet 2016;387:229e238. [5] Valdya JS, Wenz F, Bulsara M, et al. Risk adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGITA randomized trial. Lancet 2014;383:603e613. [6] Veronesi U, Orecchia R, Maisonneuve P, et al. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): A randomised controlled equivalence trial. Lancet Oncol 2013;14: 1269e1277. [7] Marta GN, Macedo CR, Carvalho HA, et al. Accelerated partial irradiation for breast cancer: Systematic review and meta-analysis of 8653 women in eight randomized trials. Radiother Oncol 2015;14: 42e49. [8] Smith BD, Arthur DW, Buchholz TA, et al. Accelerated partial breast irradiation consensus statement from the American society for radiation oncology (ASTRO). Int J Radiat Oncol Biol Phys 2009;74:987e 1001. [9] Polgar C, Van Limbergen W, P€otter R, et al. Patient selection for accelerated partial breast irradiation (APBI) after breast conserving surgery: Recommendations of the Groupe Europeen de Curietherapie- European society for therapeutic radiology and oncology (GEC-ESTRO) breast cancer working group. Radiother Oncol 2010;94:234e273. [10] Shah C, Vicini F, Wazer DE, et al. The American Brachytherapy Society consensus statement for accelerated partial breast irradiation. Brachytherapy 2013;12:267e277. [11] Petera J, Soumarova R, R uzickova J, et al. Perioperative hyperfractionated high-dose rate brachytherapy for the treatment of soft
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[12]
[13]
[14]
[15]
[16]
[17]
[18]
tissue sarcomas: Multicentric experience. Ann Surg Oncol 2010;17: 206e210. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys 1995;31:1341e1346. Wazer DE, Kaufman S, Cuttino L, et al. Accelerated partial breast irradiation: An analysis of variables associated with late toxicity and long-term cosmetic outcome after high-dose-rate interstitial brachytherapy. Int J Radiat Oncol Biol Phys 2006;64:489e495. Cambeiro M, Martinez-Regueira F, Rodriguez-Spiteri N, et al. Multicatheter breast implant during breast conservative surgery: Novel approach to deliver accelerated partial breast irradiation. Brachytherapy 2016;15:458e494. Murawa P, Murawa D, Adamczyk B, et al. Breast cancer: Actual methods of treatment and future trends. Rep Pract Oncol Radiother 2014;19:165e172. Sharma DN, Deo SVS, Rath GK, et al. Perioperative high-dose rate interstitial boost for patients with early breast cancer. Tumori 2013; 99:604e610. Belkacemi Y, Chauver MP, Giard S, et al. Partial breast irradiation as sole therapy for low risk breast carcinoma: early toxicity, cosmesis and quality of life results of a MammoSite brachytherapy. Radiother Oncol 2009;90:23e29. Aristei C, Palumbo I, Cucciarelli F, et al. Partial breast irradiation with interstitial high-dose - rate brachytherapy in early breast cancer: Results of a phase II prospective study. Eur J Surg Oncol 2009;35: 144e150.
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[19] Sedlmayer F, SauttereBihl ML, Budach W, et al. DFEGRO practical guidelines : Radiotherapy of breast cancer I. Strahlenther Onkol 2013;10:825e833. [20] Dolezel M, Stastny K, Odrazka K, et al. Perioperative interstitial CTbased brachytherapy boost in breast cancer opatients with breast conservation after neoadjuvant chemotherapy. Neoplasma 2012;59:494e499. [21] Strnad V, Hildebrandt G, P€otter R, et al. Accelerated partial breast irradiation: 5eyear results of the German-Austrian multicentre phase II trial using interstitial multicatheter brachytherapy alone after breast-conserving surgery. Int J Radiat Oncol Biol Phys 2011;80: 17e24. [22] Ott OJ, Strnad V, Hildebrandt G, et al. GEC-ESTRO multicentre phase 3-trial: Accelerated partial breast irradiation with interstitial multicatheter brachytherapy versus external beam whole breast irradiation: Early toxicity and patients compliance. Radiother Oncol 2016;120:119e123. [23] Polgar C, Hildebrand G, Kauer Dorner D, et al. Late side-effects and cosmetic result of accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation after breastconserving surgery for low.risk invasive and in-situ carcinoma of the female breast: 5-year results of a randomized, controlled, phase 3 trial. Lancet Oncol 2017;18:259e268. [24] Antonucci JV, Wallace M, Goldstein NS, et al. Differences in patterns of failure in patients treated with accelerated partial breast irradiation versus whole-breast irradiation: A matched-pair analysis with 10 year follow-up. Int J Radiat Oncol Biol Phys 2009;74:447e452. [25] Cancer incidence in the czech republic. Prague, Czech Republic: 2015. UZIS CR;