CyberKnife versus multicatheter interstitial brachytherapy for accelerated partial breast irradiation: a dosimetrical assessment with focus on organs at risk.

Background: The purpose of the study was to dosimetrically compare multicatheter interstitial brachytherapy (MIBT) and stereotactic radiotherapy with CyberKnife (CK) for accelerated partial breast irradiation with special focus on dose to organs at risk (OARs). Materials and methods: Treatment plans of thirty-one patients treated with MIBT were selected and additional CK plans were created on the same CT images. The OARs included ipsilateral non-target and contralateral breast, ipsilateral and contralateral lung, skin, ribs, and heart for left sided cases. The fractionation was identical (4 × 6.25 Gy). Dose-volume parameters were calculated for both techniques and compared. Results: The D90 of the PTV for MIBT and CK were similar (102.4% vs. 103.6%, p = 0.0654), but in COIN the MIBT achieved lower value (0.75 vs. 0.91, p < 0.001). Regarding the V100 parameter of non-target breast CK performed slightly better than MIBT (V100: 1.1% vs. 1.6%), but for V90, V50 and V25 MIBT resulted in less dose. Every examined parameter of ipsilateral lung, skin, ribs and contralateral lung was significantly smaller for MIBT than for CK. Protection of the heart was slightly better with MIBT, but only the difference of D2cm3 was statistically significant (17.3% vs. 20.4%, p = 0.0311). There were no significant differences among the dose-volume parameters of the contralateral breast. Conclusion: The target volume can be properly irradiated by both techniques with high conformity and similar dose to the OARs. MIBT provides more advantageous plans than CK, except for dose conformity and the dosimetry of the heart and contralateral breast. More studies are needed to analyze whether these dosimetrical findings have clinical significance.

Accelerated partial breast irradiation by brachytherapy: present evidence and future developments.

Accelerated partial breast irradiation (APBI) delivers a short course of adjuvant RT after breast conserving surgery to only a limited part of the breast where the tumor was located. This procedure requires expertise, good communication, and close collaboration between specialized surgeons and attending radiation oncologists with adequate intraoperative tumor bed clip marking. However, APBI offers several intrinsic benefits when compared with whole breast irradiation (WBIR) including reduced treatment time (1 versus 4-6 weeks) and better sparing of surrounding healthy tissues. The present publication reviews the APBI level 1-evidence provided with various radiation techniques supplemented by long-term experience obtained from large multi-institutional phase II studies. Additionally, it offers an outlook on recent research with ultra-short or single-fraction APBI courses and new brachytherapy sources. Mature data from three randomized controlled trials (RCTs) clearly prove the noninferiority of APBI with 'only two techniques-1/MIBT (multicatheter interstitial brachytherapy) (two trials) and 2/intensity modulated radiotherapy (one trial)'-in terms of equivalent local control/overall survival to the previous standard 'conventionally fractionated WBIR'. However, MIBT-APBI techniques were superior in both toxicity and patient-reported outcomes (PROs) versus WBIR at long-term follow-up. Currently, in RCT-setting, alternative APBI techniques such as intraoperative electrons, 50-kV x-rays and three-dimensional conformal external beam radiotherapy (3D-CRT) failed to demonstrate noninferiority to conventionally fractionated WBIR. However, 3D-CRT-APBI compared noninferior to hypo-fractionated WBIR in preventing ipsilateral breast tumor recurrence (randomized RAPID-trial) but was associated with a higher rate of late radiation toxicity. Ultimately, MIBT remains the only APBI modality with noninferior survival/superior toxicity/PROs at 10-years and therefore should be prioritized over alternative methods in patients with breast cancer considered at low-risk for local recurrence according to recent international guidelines.

Preliminary report on ultrashort perioperative partial-breast irradiation with multicatheter interstitial brachytherapy for early-stage breast cancer.

PURPOSE: Perioperative partial-breast irradiation (PBI) with multicatheter interstitial brachytherapy (MIB) is less invasive and more convenient than postoperative one. This study aimed to compare ultrashort perioperative MIB-PBI (uPBI) and conventional perioperative MIB-PBI (cPBI) performed during the same period of time. METHODS: Inclusion criteria of the study were patients aged ≥ 40 years and those with T0-2 (≤ 3 cm), N0-mi, and negative margins on mammography. The locoregional recurrence (LRR) and toxicity rates were compared between uPBI at a dose of 25.2 Gy in four fractions and cPBI at a dose of 32 Gy in eight fractions. RESULTS: In total, 198 patients (151 with uPBI and 47 with cPBI) were evaluated. At a median follow-up of 20.1 months, one (0.66%) patient in the uPBI group had LRR. The 2-year ipsilateral breast tumor recurrence-free survival rates of the uPBI and cPBI groups were 98.7% and 100%, respectively. The highest toxicity grades were grade 1 in 23 (15.2%) and grade 2 in 2 (1.3%) patients in the uPBI group, and grade 1 in 8 (17.0%) and grade 2 in 1 (2.1%) patient in the cPBI group. None of the patients in the two groups presented with grade 3 and higher toxicities. The toxicity rates between the two groups did not significantly differ. Further, 22 (14.6%) patients in the uPBI group and 8 (17.0%) in the cPBI group, and 3 (2.0%) patients in the uPBI group and 1 (2.1%) in the cPBI had acute and late toxicities, respectively. The timing of toxicity development between the two groups did not significantly differ. CONCLUSIONS: Although this preliminary report included a small sample size and had a short follow-up period, the local control and toxicity rates were similar between the uPBI and cPBI groups. Further research is warranted to investigate the ideal dose schedule of MIB-PBI.

A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using multicatheter interstitial brachytherapy: clinical results with a median follow-up of 60 months.

BACKGROUND: We carried out the first multi-institutional prospective study on accelerated partial breast irradiation (APBI) via multicatheter interstitial brachytherapy in a shorter period for early breast cancer in Japan. METHODS: Patient eligibility criteria included positive hormone receptors, tumors ≤ 3 cm and TNM stage pN0M0. After breast-conserving surgery (Japanese cylindrical resection) and histological confirmation of negative surgical margins and the absence of lymph node metastasis, applicator implantation was performed either postoperatively or intraoperatively. High-dose-rate brachytherapy of 36 Gy in 6 fractions was delivered. RESULTS: Forty-six patients from six institutions received this treatment regimen, and the median follow-up time was 60 months (range 57-67 months). The median resected breast tissue volume was 81 cm3 (range 28-260 cm3). No Grade 4 late sequela, local recurrence nor death due to breast cancer were observed. Grade 2-3 sequelae such as rib fracture (2%), soft tissue necrosis (9%), fibrosis (20%), and breast pain (9%) were observed. The resected breast tissue volumes of the patients who had Grade ≥ 2 fibrosis and Grade < 2 fibrosis were 105.9 ± 32.3 cm3 and 76.3 ± 45.6 cm3, respectively, p = 0.02. The overall cosmetic outcome score of Excellent/Good was 74% at 60 months after APBI. Grade ≥ 1 fibrosis was observed in 44% and 92% of patients who scored Excellent/Good and Fair/Poor, respectively, p = 0.004. CONCLUSIONS: This study showed excellent local control and survival results with minimal late sequelae.

Multicatheter interstitial brachytherapy versus stereotactic radiotherapy with CyberKnife for accelerated partial breast irradiation: a comparative treatment planning study with respect to dosimetry of organs at risk.

BACKGROUND: The aim of the study was to dosimetrically compare multicatheter interstitial brachytherapy (MIBT) and stereotactic radiotherapy with CyberKnife (CK) for accelerated partial breast irradiation (APBI) especially concerning the dose of organs at risk (OAR-s). PATIENTS AND METHODS: Treatment plans of thirty-two MIBT and CK patients were compared. The OAR-s included ipsilateral non-target and contralateral breast, ipsilateral and contralateral lung, skin, ribs, and heart for left-sided cases. The fractionation was identical (4 x 6.25 Gy) in both treatment groups. The relative volumes (e.g. V100, V90) receiving a given relative dose (100%, 90%), and the relative doses (e.g. D0.1cm3, D1cm3) delivered to the most exposed small volumes (0.1 cm3, 1 cm3) were calculated from dose-volume histograms. All dose values were related to the prescribed dose (25 Gy). RESULTS: Regarding non-target breast CK performed slightly better than MIBT (V100: 0.7% vs. 1.6%, V50: 10.5% vs. 12.9%). The mean dose of the ipsilateral lung was the same for both techniques (4.9%), but doses irradiated to volume of 1 cm3 were lower with MIBT (36.1% vs. 45.4%). Protection of skin and rib was better with MIBT. There were no significant differences between the dose-volume parameters of the heart, but with MIBT, slightly larger volumes were irradiated by 5% dose (V5: 29.9% vs. 21.2%). Contralateral breast and lung received a somewhat higher dose with MIBT (D1cm3: 2.6% vs. 1.8% and 3.6% vs. 2.5%). CONCLUSIONS: The target volume can be properly irradiated by both techniques with similar dose distributions and high dose conformity. Regarding the dose to the non-target breast, heart, and contralateral organs the CK was superior, but the nearby organs (skin, ribs, ipsilateral lung) received less dose with MIBT. The observed dosimetric differences were small but significant in a few parameters at the examined patient number. More studies are needed to explore whether these dosimetric findings have clinical significance.

Predicting adherence of dose-volume constraints for personalized partial-breast irradiation technique.

PURPOSE: Multicatheter interstitial brachytherapy (MIB) and external-beam (EB) radiotherapy are established partial-breast irradiation (PBI) techniques. Although EB-PBI is widely available, it requires extra irradiated margins for target uncertainties. We examined the impact of EB-PBI on dose-volume constraints as compared to MIB-PBI. METHODS AND MATERIALS: Among 653 patients receiving MIB-PBI between October 2008 and April 2020, consequent 159 patients after September 2018 were examined. Clinical target volume (CTV) included the lumpectomy cavity plus 1.0 cm. Planning target volume (PTV) for EB-PBI was defined as CTV with 1.0-cm expansion. Because the ratio of PTV to breast volume (RPB) was related to cosmesis, <25% of RPB was defined as suitable for the ipsilateral breast constraints. Preoperative breast size was classified as very small (<350 cm3), small (350-699 cm3), and medium or large (≥700 cm3). According to each category, the dose-volume constraints of the organs at risk were compared between the two PBI techniques. RESULTS: Patients including 84 very small, 59 small, and 16 moderate to large breasts were examined. Although RPB was suitable in all patients receiving MIB-PBI, it was achieved in 74 patients (46.5%) receiving EB-PBI (p < 0.0001). The suitable RPB in patients with very small, small, and moderate to large breast was 32.1%, 55.9%, and 100%, respectively (p < 0.0001). Normal-tissue constraints for the other organs could be satisfied in patients with moderate to large breasts. CONCLUSION: Although EB-PBI may be an appropriate option for patients with moderate to large breasts, MIB-PBI could still be a crucial technique, especially for patients with small breasts.

Endocrine therapy with accelerated Partial breast irradiatiOn or exclusive ultra-accelerated Partial breast irradiation for women aged ≥ 60 years with Early-stage breast cancer (EPOPE): The rationale for a GEC-ESTRO randomized phase III-controlled trial.

PURPOSE: Breast cancer in the elderly has become a public health concern; there is a need to re-design its treatment with a view to de-escalation. Our paper sets out the rationale for a phase 3 randomized trial to evaluate less burdensome adjuvant procedures that remain effective and efficient. MATERIALS AND METHODS: For low-risk breast cancer in the elderly, adjuvant treatment has been adjusted in order to make it more suitable and efficient. Hypofractionated radiation therapy based on accelerated or non-accelerated regimens as well as accelerated and ultra-accelerated partial breast irradiation (APBI) protocols were reviewed. Withdrawal of radiation (RT) or endocrine therapies (ET) from the adjuvant procedure were also investigated. Based on molecular and APBI classifications, inclusion criteria were discussed. RESULTS: Phase 3 randomized trials which compared standard vs. accelerated/non-accelerated hypofractionated regimens confirmed that the latter were non-inferior in terms of local control. Similarly, except for intraoperative-based techniques, APBI achieved non-inferior local control rates compared to whole breast irradiation for low-risk breast cancer. In phase 2 prospective trials using ultra APBI, encouraging results were observed regarding oncological outcome and toxicity profile. In phase 3 trials, adjuvant ET without RT significantly increased the rate of local relapse with no impact on overall survival while RT alone proved effective. Elderly patients aged 60 or more with low-risk, luminal A breast cancer were chosen as the target population in a phase 3 randomized trial comparing APBI + 5-year ET vs. uAPBI (16 Gy 1f) alone. CONCLUSION: To investigate de-escalation adjuvant treatment for elderly breast cancer patients, we have defined a road map for testing more convenient strategies. This EPOPE phase 3 randomized trial is supported by the GEC-ESTRO breast cancer working group.

Catheter-based delineation of lumpectomy cavity for accurate target definition in partial-breast irradiation with multicatheter interstitial brachytherapy.

PURPOSE: In partial-breast irradiation (PBI), accurate lumpectomy cavity (LC) delineation is critical. Seroma-based delineation (SBD) using computed tomography (CT) with clips remains uncertain, causing an expansion of the LC and planning target volume (PTV). In catheter-based delineation (CBD), the implanted catheters were used as reference markers for LC delineation in multicatheter interstitial brachytherapy (MIB). MATERIAL AND METHODS: Between October 2008 and October 2018, 513 patients who underwent MIB-PBI were examined. In CBD, anatomical relations of LC to catheters were recorded. In randomly selected 22 CBD cases, the LC volume and PTV were retrospectively recontoured on SBD, and the relationship between the contribution of CBD and cavity visuality was evaluated. The LC volume and PTV before and after the introduction of CBD were compared. RESULTS: The mean LC volumes based on SBD and CBD were 19.1 cm3 and 14.1 cm3, respectively (p < 0.001). The mean PTVs based on SBD and CBD were 47.9 cm3 and 35.7 cm3, respectively (p < 0.0001). More reductions in the LC volume (5.1 cm3) (p < 0.05) and PTV (7.7 cm3) (p = 0.13) were observed in the poorly visible LC than in the visible LC. The LC volume and PTV before the introduction of CBD (n = 411) were compared with those after introduction (n = 102). Significant reductions were observed in the LC volume (5.9 cm3) (p < 0.0001) after the introduction of CBD; moreover, PTV tended to be reduced (3.9 cm3) (p = 0.17). CONCLUSIONS: CBD may help to establish the standardized procedure for MIB-PBI and prevent unnecessary radiation exposure to the normal breast tissue.

Moving incision for covert breast-conserving surgery may prevent early wound complications in brachytherapy-based partial-breast irradiation.

PURPOSE: Brachytherapy-based partial-breast irradiation (PBI) is a treatment option for breast-conserving therapy. Although intraoperative catheter implantation has been introduced, early wound complications are a concern. Covert operations with a moving incision are widely performed to hide surgical scars and may reduce the incision-site radiation dose. This study aimed to compare complication rates for moving incision and conventional incision in covert breast-conserving surgery. METHODS AND MATERIALS: Between October 2008 and December 2018, the medical records of all patients who underwent PBI using multicatheter interstitial brachytherapy after breast-conserving surgery were examined. Since July 2016, to hide the scar, we have performed a moving incision from above the tumor to an invisible site at our institution. The planning target volume included 1.0-1.5 cm of tissue surrounding the surgical cavity. High-dose-rate interstitial brachytherapy with a dose of 32 Gy in eight fractions was performed. The cumulative incidences of surgical site infections and symptomatic seromas ≤90 days were analyzed. RESULTS: The study included 516 consecutive patients with 526 lesions. Overall, 40 (7.6%) early wound complications were observed, in which 4 (2.6%) involved 152 moving incisions and 36 (9.6%) involved 374 conventional incisions (p = 0.01). On univariate analysis, age, tumor diameter, re-excision, planning target volume, numbers of catheters and planes, and incision type were risk factors for complications. On multivariate analysis, only incision type was a risk factor. Moving incision reduced the early complication rate by 75% (p = 0.01). CONCLUSION: Moving incision in covert breast-conserving surgery reduced the risk of early wound complications.

Should molecular subtype be recommended as one of the selection criteria for accelerated partial breast irradiation? Preliminary results from an Asian cohort.

PURPOSE: The purpose of this study was to report clinical outcomes in patients treated with accelerated partial breast irradiation (APBI), stratified as per molecular subtype and American Society for Therapeutic Radiology and Oncology/Groupe Européen de Curiethérapie and European Society for Radiotherapy & Oncology (ASTRO/GEC-ESTRO) patient selection criteria in order to determine whether molecular subtype should be recommended as one of the selection criteria for APBI. MATERIAL AND METHODS: 157 early-stage breast cancers patients, treated with APBI using multi-catheter interstitial brachytherapy with ≥ 6 months follow-up were included. Molecular subtype was assigned based on estrogen/progesterone receptor (ER/PR), Her2neu and tumor grade. Patients were stratified into ASTRO and GEC-ESTRO risk groups, as per updated ASTRO consensus statement (CS) and GEC-ESTRO recommendation, respectively. The Kaplan-Meier method was used to calculate the time to event data of clinical outcomes. RESULTS: With a median follow-up of 35 months, local control (LC) and locoregional control (LRC) were not significantly different among the different molecular subtypes (p = 0.19, p = 0.41, respectively). None of the APBI guidelines predicted risk of local or locoregional recurrence. Re-analyzing the data by replacing ER status with molecular subtype in the ASTRO-CS did not show any significant difference in LC/LRC across the various categories. Her2neu subtype was associated with significantly lower disease-free survival, cause specific survival, and overall survival than the luminal subtypes. CONCLUSIONS: None of the mentioned APBI guidelines predicted local or locoregional recurrence risk in our study population. Additional follow-up will be needed to recommend inclusion of molecular subtype (or at least HER2 receptor status) in the patient selection criteria for APBI.

Impact of inter-observer variations in target volume delineation on dose volume indices for accelerated partial breast irradiation with multi-catheter interstitial brachytherapy.

PURPOSE: To investigate dosimetric impact of inter-observer variation in clinical target volume(CTV) delineation for patients undergoing interstitial partial breast brachytherapy. METHODS: Five radiation oncologists delineated CTV in twenty patients who underwent multi-catheter partial breast brachytherapy. Five treatment plans for each patient were graphically optimized for CTV of all observers and evaluated using coverage index(CI), external volume index(EI), overdose volume index(OI) and conformal index(COIN). In addition, volume enclosed by prescription isodose(V100), its spatial concordance(CIcommon), mean coverage of all CTVs with common volume of prescription dose(V100_common) and mean CTV coverage for all pairs of observer with common prescription volume of respective pairs(V100_pair) were also computed. RESULTS: The mean ±â€¯standard deviation(SD) of CI and COIN ranged from 0.756 ±â€¯0.076 to 0.840 ±â€¯0.070 and 0.591 ±â€¯0.090 to 0.673 ±â€¯0.06 respectively. When a plan made for CTV of individual observer was evaluated on CTV of all observers, the maximum variations(ρ < 0.05) in the mean CI,COIN,OI and EI were 10.6%,11.4%,10.6% and 72.7% respectively. The observed mean ±â€¯SD of V100, CIcommon of V100, CTV coverage with V100_common and V100_pair was 160.7 ±â€¯52.1, 0.70 ±â€¯0.09, 73.1 ±â€¯8.1% and 77.9 ±â€¯7.3% respectively. CONCLUSION: Inter-observer variation in delineation of CTV showed significant dosimetric impact with mean CTV coverage of 73.1% and 77.9% by common and paired prescription dose volume respectively among all observers.

Multicatheter interstitial brachytherapy for breast cancer.

Brachytherapy remains the best irradiation technique to deliver a high dose in a small volume. Breast brachytherapy is part of the arsenal of therapy in the management of breast cancer. In this article, we present the technical data related to multicatheter interstitial brachytherapy to the breast proceeding, from the implantation of the vectors to the treatment itself. The indications for brachytherapy in breast cancer are boost after whole breast irradiation, accelerated partial breast irradiation or selected patients with second ipsilateral breast tumor event. The results in terms of efficacy and toxicity are presented for each indication. Multicatheter interstitial breast brachytherapy remains a major technique for breast cancer treatment.

Change of target volume and its dosimetric impact during the course of accelerated partial breast irradiation using intraoperative multicatheter interstitial brachytherapy after open cavity surgery.

PURPOSE: To investigate the change of clinical target volume (CTV) and its dosimetric impact during the course of accelerated partial breast irradiation (APBI) using intraoperative multicatheter interstitial brachytherapy after open cavity surgery. METHODS AND MATERIALS: Twenty-two patients of APBI with intraoperative placement of catheters underwent computed tomography scans for the treatment planning before the first (CT1) and the last (CT2) treatment fraction. Delineation of lumpectomy cavity and CTV was done consistently on both CT data sets by one of the coauthors. Optimum plan (PCT1) was made on CT1. PCT1 was manually reproduced in CT2 which yielded plan PCT2. Plans were compared using coverage index (CI), dose homogeneity index (DHI), external volume index (EI), overdose volume index (OI) and conformal index (COIN). RESULTS: The mean ± SD volume of lumpectomy cavity and CTV was 78.5 ± 40.7 cm3, 156.4 ± 69.0 cm3 for PCT1, and 84.7 ± 50.1 cm3 (p = 0.11), 165.7 ± 82.8 cm3 (p = 0.15) for PCT2, respectively. CTV volume increase by ≥ 10% was observed in 9 cases however decrease of ≥10% was observed in 5 cases. Mean (SD) of absolute pairwise difference in CTV volume was found to be 13.2 (6.7) %. For cases with increase in CTV volume, significant (p < 0.05) decrease of 8.4%, 12.2%, and 5.5% was observed in CI, EI, and COIN of CTV respectively. However for cases with shrinkage of CTV, significant (p = 0.004) increase of 45% in EI was observed, whereas COIN reduced significantly (p = 0.001) by 13.5%. Overall 22 cases showed significant decrease of 5.8% and 8.1% in mean CI and COIN, respectively. CONCLUSIONS: The change of CTV during the course of APBI using intraoperative multicatheter interstitial brachytherapy after open cavity surgery was found patient specific and showed a significant impact on coverage and conformity.