Detection of setup errors with a body-surface laser-scanning system for whole-breast irradiation after breast-conserving surgery.

PURPOSE: We compared the setup errors determined by an optical imaging system (OSIS) in women who received breast-conserving surgery (BCS) followed by whole-breast radiotherapy (WBRT) with those from cone-beam computed tomography (CBCT) carried out routinely. METHODS: We compared 130 setup errors in 10 patients undergoing WBRT following BCS by analyzing the translational and rotational couch shifts via CBCT and OSIS. Patients were treated with intensity-modulated radiotherapy (IMRT). The patient outline extracted from the planning reference Computed tomography (CT) was used as the reference for OSIS and CBCT alignment during treatment. We detected the setup uncertainty using CBCT and OSIS at the first five fractionations of RT and then twice a week. RESULTS: The absolute translational setup error (mean ± Standard deviation (SD)) in x (lateral), y (longitudinal), and z (vertical) axes detected by the OSIS was 0.14 ± 0.18, 0.15 ± 0.14, and 0.13 ± 0.13 cm, respectively. The rotational setup error (mean ± SD) in Rx (pitch), Ry (roll), and Rz (yaw) axes was 0.77 ± 0.54, 0.76 ± 0.61, and 1.23 ± 0.95, respectively. Significant difference is observed only in one direction (Rx, p = 0.03) in the paired setup errors obtaining from OSIS and CBCT, without significant differences in five directions. CONCLUSION: OSIS is a repeatable and reliable system that can be used to detect misalignments with accuracy, which is capable of supplementing CBCT for WBRT after BCS. We believe that an OSIS may be easier to use, quicker, and reduce overall dose as this method of patient alignment does not require ionizing radiation.

Analysis of breast cosmetic effects 3 years after breast-conserving surgery and intraoperative radiotherapy with and without adjuvant whole breast irradiation.

INTRODUCTION: Intraoperative radiotherapy (IORT) based on low-kV photons may be an option for early breast cancer patients. Following Targit trial results some of those patients should undergo whole breast irradiation (WBRT) additionally. MATERIAL AND METHODS: Since April 2010, IORT has been applied to early breast cancer patients. One hundred and fifty patients were prospectively followed up and examined to evaluate the side effects (pain, fibrosis, breast edema, telangiectasias). We present the results 3 years post-treatment. WBRT was given to 82 (54.7%) patients. RESULTS: Tumor cavity fibrosis grade II and more was observed in 18 (12%) patients, as grade III only in 2 (1.33%) patients. Breast tissue fibrosis outside tumor cavity grade II was observed only in 2 (1.33%) patients. Breast edema was present in 10 (6.66%) patients. WBRT administration led to increased frequency of higher grade tumor cavity fibrosis (P < .0001), breast fibrosis (P < .0001), breast edema (P = .003), and occurrence of telangiectasias (P = .03), with no influence on pain reported by patients. In case of WBRT, tumor location (P = .026) and size of the irradiated breast (P = .015) were independent risk factors for higher degree of breast fibrosis, as seroma evacuation 6 months post-WBRT (P = .036) was the only independent risk factor for higher level of tumor cavity fibrosis in multiple regression. CONCLUSIONS: The cosmetic result after IORT is good and comparable to other accelerated partial breast irradiation techniques. Administration of WBRT post-IORT in breast cancer patients increases the level of fibrotic changes, breast edema and telangiectasias 3 years post-treatment, but with no influence on pain.

A study of the dosimetric impact of daily setup variations measured with cone-beam CT on three-dimensional conformal radiotherapy for early-stage breast cancer delivered in the prone position.

PURPOSE: To evaluate the dosimetric impact of daily positioning variations measured with cone-beam computed tomography (CBCT) on whole-breast radiotherapy patients treated in the prone position. METHODS: Daily CBCT was prospectively acquired for 30 consecutive patients positioned prone. Treatment for early-stage (≤II) breast cancer was prescribed with standard dose (50 Gy/25 fractions) or hypofractionation (42.56 Gy/16 fractions) for 13 and 17 patients, respectively. Systematic and random errors were calculated from the translational CBCT shifts and used to determine population-based setup margins. Mean translations (±one standard deviation) for each patient were used to simulate the dosimetric impact on targets (PTV_eval and lumpectomy cavity), heart, and lung. Paired Student's t tests at α = 0.01 were used to compare dose metrics after correction for multiple testing (P < 0.002). Significant correlation coefficients were used to identify associations (P < 0.01). RESULTS: Of 597 total fractions, 20 ± 13% required patient rotation. Mean translations were 0.29 ± 0.27 cm, 0.41 ± 0.34 cm, and 0.48 ± 0.33 cm in the anterior-posterior, superior-inferior, and lateral directions leading to calculated setup margins of 0.63, 0.88, and 1.10 cm, respectively. Average three-dimensional (3D) shifts correlated with the maximum distance of breast tissue from the sternum (r = 0.62) but not with body-mass index. Simulated shifts showed significant, but minor, changes in dose metrics for PTV_eval, lung, and heart. For left-sided treatments (n = 18), mean heart dose increased from 109 ± 75 cGy to 148 ± 115 cGy. Shifts from the original plan caused PTV_eval hotspots (V105%) to increase by 5.2% ± 3.8%, which correlated with the total MU of wedged fields (r = 0.59). No significant change in V95% to the cavity was found. CONCLUSIONS: Large translational variations that occur when positioning prone breast patients had small but significant dosimetric effects on 3DCRT plans. Daily CBCT may still be necessary to correct for rotational variations that occur in 20% of treatments. To maintain planned dose metrics, unintended beam shifts toward the heart and the contribution of wedged fields should be minimized.

Patient preferences regarding intraoperative versus external beam radiotherapy for early breast cancer and the impact of socio-demographic factors.

PURPOSE: Patient comfort and preference have steadily gained attention in radio-oncologic treatment of breast cancer. Therefore, the purpose of this investigation was to further explore patient preferences in choosing between intraoperative radiotherapy (IORT) and external beam radiotherapy (EBRT). METHODS: We prospectively analysed data of 101 women, who were candidates for breast-conserving surgery with adjuvant radiotherapy. A two-part video was shown to patients: an educational section about EBRT/IORT, followed by a preference elicitation section focusing on additional accepted risk (AAR) of recurrence after either treatment. Furthermore, participants completed a questionnaire to identify factors that influence patient preference of radiation modality. RESULTS: The data demonstrate that 42.5% of patients would accept additional risk of recurrence for IORT versus 9% AAR for EBRT, while 48.5% of patients would not accept any additional risk, yet would choose IORT over EBRT if risks of recurrence were equivalent. When combining patient preferences and the results from the questionnaire, no single socio-economic/-demographic factor was found to significantly correlate with AAR of IORT. CONCLUSION: Our study confirms the existence of subgroups of breast cancer patients who would accept an additional risk of recurrence associated with choice of radiation modality to receive a single dose of IORT as adjuvant radiotherapy for breast cancer instead of EBRT over several weeks; yet our data fail to identify a single factor significantly associated with these patient preferences and, therefore, helpful for individualised decision-making processes.

Radiotherapy setup displacements in breast cancer patients: 3D surface imaging experience.

AIM: In this study, we intend to compare two different setup procedures for female breast cancer patients. BACKGROUND: Imaging in radiotherapy provides a precise localization of the tumour, increasing the accuracy of the treatment delivery in breast cancer. MATERIALS AND METHODS: Twenty breast cancer patients who underwent whole breast radiotherapy (WBRT) were selected for this study. Patients were divided into two groups of ten. Group one (G1) was positioned by tattoos and then the patient positioning was adjusted with the aid of AlignRT (Vision RT, London, UK). In group two (G2), patients were positioned only by tattoos. For both groups, the first 15 fractions were analyzed, a daily kilovoltage (kV) cone beam computed tomography (CBCT) image was made and then the rotational and translational displacements and, posteriorly, the systematic (Σ) and random (σ) errors were analyzed. RESULTS: The comparison of CBCT displacements for the two groups showed a statistically significant difference in the translational left-right (LR) direction (ρ = 0.03), considering that the procedure with AlignRT system has smaller lateral displacements. The results of systematic (Σ) and random (σ) errors showed that for translational displacements the group positioned only by tattoos (G2) demonstrated higher values of errors when compared with the group positioned with the aid of AlignRT (G1). CONCLUSIONS: AlignRT could help the positioning of breast cancer patients; however, it should be used with another imaging method.

Multi-centre real-world validation of automated treatment planning for breast radiotherapy.

PURPOSE: To present the results of the first multi-centre real-world validation of autoplanning for whole breast irradiation after breast-sparing surgery, encompassing high complexity cases (e.g. with a boost or regional lymph nodes) and a wide range of clinical practices. METHODS: The 24 participating centers each included 10 IMRT/VMAT/Tomotherapy patients, previously treated with a manually generated plan ('manplan'). There were no restrictions regarding case complexity, planning aims, plan evaluation parameters and criteria, fractionation, treatment planning system or treatment machine/technique. In addition to dosimetric comparisons of autoplans with manplans, blinded plan scoring/ranking was conducted by a clinician from the treating center. Autoplanning was performed using a single configuration for all patients in all centres. Deliverability was verified through measurements at delivery units. RESULTS: Target dosimetry showed comparability, while reductions in OAR dose parameters were 21.4 % for heart Dmean, 16.7 % for ipsilateral lung Dmean, and 101.9 %, 45.5 %, and 35.7 % for contralateral breast D0.03cc, D5% and Dmean, respectively (all p < 0.001). Among the 240 patients included, the clinicians preferred the autoplan for 119 patients, with manplans preferred for 96 cases (p = 0.01). Per centre there were on average 5.0 ± 2.9 (1SD) patients with a preferred autoplan (range [0-10]), compared to 4.0 ± 2.7 with a preferred manplan ([0,9]). No differences were observed regarding deliverability. CONCLUSION: The automation significantly reduced the hands-on planning workload compared to manual planning, while also achieving an overall superiority. However, fine-tuning of the autoplanning configuration prior to clinical implementation may be necessary in some centres to enhance clinicians' satisfaction with the generated autoplans.

Sequential Moderate Hypofractionated Boost in Breast Cancer Patients: A Monoinstitutional Analysis of Late Side Effects.

BACKGROUND/AIM: In breast cancer (BC) patients who have received breast-conserving surgery, moderate hypofractionation is standard of care for whole-breast irradiation (HF-WBI). On the other hand, the fractionation schedule for the boost is less well defined. A previous prospective study of our group aimed at evaluating acute and late cutaneous and subcutaneous side effects related to a sequential hypofractionated boost (HB) in patients who had received HF-WBI. The present study aimed at evaluating late side effects at a longer follow-up. PATIENTS AND METHODS: From 2014 to 2015, 219 BC patients received moderate HF-WBI (42.4 Gy in 16 fractions) at the Radiation Oncology Section of the University of Perugia. Patients with negative prognostic factors received a HB (2.65 Gy for 4 or 5 fractions). Late side effects were assessed using the Common Terminology Criteria for Adverse Events v5.0. Univariate and multivariate analyses estimated predictive factors for late toxicity. RESULTS: Median follow-up was 8.6 years (range=6.7-9.6). One hundred and sixty-five patients were evaluable in the present analysis; HB was administered to 47.3% of them. Late cutaneous and subcutaneous side effects occurred in 26/165 patients (15.8%); and all were G1. In univariate analysis ≥10 excised lymph nodes and HB administration emerged as risk factors for late side effects (p=0.003 and p=0.041, respectively). In multivariate analysis only ≥10 excised lymph nodes were confirmed as a risk factor for side effects (OR=3.431; 95%CI=1.209-9.737). CONCLUSION: HB after HF-WBI was safe and well-tolerated, even at a long-term follow-up; consequently, it can be used in routine practice.

Comparison of mammography and ultrasound findings in the follow-up of patients with breast cancer treated with segmental mastectomy followed by intraoperative electron radiotherapy versus external whole breast radiotherapy

PURPOSE: This study aims to describe imaging findings in patients treated with intraoperative electron radiotherapy and compare them with those detected in patients treated with external whole breast radiotherapy (WBRT). METHODS: The study population consisted of 25 patients who received intraoperative radiotherapy [IORT (21 Gy)] as single-dose radiotherapy and a control group of 25 patients who received WBRT at the same institution. Mammography and ultrasound (US) findings were divided into three groups: minor, intermediate, and advanced. On mammography, mass lesions were considered advanced, and asymmetries or architectural distortions were considered intermediate. Oil cysts, linear scars, and the increase in parenchymal density were considered minor findings. On US, irregular non-mass lesions were considered advanced, and circumscribed hypoechoic lesions or planar irregular scars with shadowing were considered intermediate. Oil cysts, fluid collections, or linear scars were considered minor findings. RESULTS: On mammography, skin thickening (P = 0.001), edema (P < 0.001), increased parenchymal density (P < 0.001), dystrophic calcifications (P = 0.045), and scar/distortion (P = 0.005) were significantly more common in the WBRT group. On US, irregular non-mass lesions, which made interpretation considerably difficult, were significantly more common in the IORT group (P = 0.004). Dominant US findings were fluid collections and postoperative linear or planar scars in the WBRT group. Minor findings were more common in low-density breasts, and major findings (intermediate and advanced) were more common in high-density breasts on both mammographies (P = 0.011) and US (P = 0.027) in the IORT group. CONCLUSION: Ill-defined non-mass lesions detected on US in the IORT group have not been defined previously. Radiologists should be aware of these lesions because they can be confusing, especially in early follow-up studies. This study has found that minor findings are seen more frequently in low-density breasts, while major findings are more common in high-density breasts in the IORT group. This has not been reported before, and further studies with more cases are needed to verify these results.

Extramedullary Relapse of B Cell Acute Lymphoblastic Leukemia in Bilateral Breasts Treated with Whole Breast Radiotherapy.

Isolated extramedullary relapse of acute lymphoblastic leukemia (ALL) in the breast is extremely rare. We herein report a case of a 38-year-old female with B cell ALL, who had isolated extramedullary relapse initially in the left breast and subsequently in the right breast, 3 and 4 years, respectively, after hematopoietic allogenic stem cell transplantation. She was successfully salvaged with bilateral whole breast radiotherapy, 24 Gy/12 fractions/2.5 weeks. This brief report highlights the importance of awareness of extramedullary leukemic relapse in the breast as one of the differential diagnoses of breast masses in the context of ALL. Since these tumors are extremely radioresponsive, radiation therapy is a safe and effective treatment option for isolated extramedullary relapse of ALL in the breast.

Long-Term Outcomes of an International Cooperative Study of Intraoperative Radiotherapy Upfront Boost With Low Energy X-Rays in Breast Cancer.

Purpose: The purpose of this study was to assess the effectivity of upfront kilovoltage intraoperative radiotherapy (IORT) as a boost in high-risk early-stage breast cancer patients from an international pooled cohort. Materials/Methods: Patients from four centers in three different countries were retrospectively screened. Those with a minimum 1-year follow-up were included. Cumulative local (LR), regional (RR), and distant metastasis rates (DM) were analyzed. Additionally, the estimated overall survival (OS) was assessed. The Cox regression analysis was performed to identify failure predicting factors. Results: A total of 653 patients from centers in Peru, Spain, and Germany were included. The median follow-up was 55 (12-180) months, and age was 58 (27-86) years. Clinical tumor (T) staging was T1 65.85%, T2 30.17%, and T3 3.98%. Positive margins were found in 7.9% and in-situ component in 20.06%. The median IORT dose was 20 (6-20). The median time from IORT to EBRT was 74.5 (13-364) days. An overall 3.4% (n = 22) of patients developed local recurrence at some point during follow-up. The 12-, 60-, and 120-month cumulative LR were 0.3%, 2.3%, and 7.9%, respectively. After multivariate analysis, only age <50 remained to be a significant prognostic factor for local recurrence (HR 0.19, 95% CI 0.08-0.47; p < 0.05). The 10-year estimated OS was 81.2%. Conclusion: Upfront boost with IORT yields similar local control outcomes to those EBRT-based reports. Results from prospective trials, regarding toxicity, cosmesis, and effectivity are awaited to confirm these findings.

Methods of Esthetic Assessment after Adjuvant Whole-Breast Radiotherapy in Breast Cancer Patients: Evaluation of the BCCT.core Software and Patients' and Physicians' Assessment from the Randomized IMRT-MC2 Trial.

The present analysis compares the esthetics assessment by the BCCT.core software in relation to patients' and physicians' ratings, based on the IMRT-MC2 trial. Within this trial, breast cancer patients received breast-conserving surgery (BCS) and adjuvant radiotherapy. At the baseline, 6 weeks, and 2 years after radiotherapy, photos of the breasts were assessed by the software and patients' and physicians' assessments were performed. Agreement rates of the assessments and their correlation with breast asymmetry indices were evaluated. The assessments of the software and the physicians were significantly correlated with asymmetry indices. Before and 6 weeks after radiotherapy, the patients' self-assessment was only correlated with the lower breast contour (LBC) and upward nipple retraction (UNR), while after 2 years, there was also a correlation with other indices. Only a slight agreement between the BCCT.core software and the physicians' or patients' assessment was seen, while a moderate and substantial agreement was detected between the physicians' and the patients' assessment after 6 weeks and 2 years, respectively. The BCCT.core software is a reliable tool to measure asymmetries, but may not sufficiently evaluate the esthetic outcome as perceived by patients. It may be more appropriate for a long-term follow-up, when symmetry appears to increase in importance.

Toxicity of Hypofractionated Whole Breast Radiotherapy Without Boost and Timescale of Late Skin Responses in a Large Cohort of Early-Stage Breast Cancer Patients.

AIM: To report toxicity of hypofractionated whole-breast radiotherapy in a large cohort of early-stage breast cancer (BCaients. MATERIALS AND METHODS: From 02/2009-05/2017, 1325 consecutive BCa patients were treated with 40.05 Gy/15 fractions, without boost. Median age was 62 (IQR:51.1-70.5) years. Chemotherapy was prescribed for 28% of patients, hormonal therapy for 80.3%, monoclonal antibodies for 8.2%. RESULTS: Median follow-up was 72.4 (IQR: 44.6-104.1) months. Acute RTOG toxicity was: 69.8% Grade (G) 1, 14.3% G2 and 1.7% G3. Late SOMA-LENT toxicities were: edema-hyperpigmentation (E-H): G1 28.67%, G2 4.41%, G3 0.15%; fibrosis-atrophy-telangiectasia-pain (F-A-T-P): G1 14.6%, G2 3.2%, G3 0.8%, G4 0.1%. Median time to first occurrence was 6 and 18 months, respectively. Aesthetic result after surgery was excellent in 28.7%, good in 41.5%, acceptable in 20.3% and poor in 9.5% of patients. Change in breast appearance after radiotherapy was mild in 6.9%, moderate in 2.3% and marked in 1.3% of patients. Concomitant chemotherapy, obesity, smoking, use of bolus and planning target volume (PTV) were associated with higher acute toxicity. Patients ≥55 years old were less likely to experience acute toxicity. PTV and acute G2 toxicity were associated with ≥G2 E-H. PTV, concomitant chemotherapy, hypertension and ≥G2 acute toxicity were associated with increased risk of F-A-T-P. CONCLUSION: Hypofractionated whole-breast radiotherapy without boost demonstrated mild acute and late toxicity in a large cohort of consecutive patients. Moderate and marked changes in breast appearance were registered for 3.6% of patients and occurred between 18 to 42 months.

Comparison of dose distributions and organs at risk (OAR) doses in conventional tangential technique (CTT) and IMRT plans with different numbers of beam in left-sided breast cancer.

AIM: Our aim was to improve dose distribution to the left breast and to determine the dose received by the ipsilateral lung, heart, contralateral lung and contralateral breast during primary left-sided breast irradiation by using intensity modulated radiotherapy (IMRT) techniques compared to conventional tangential techniques (CTT). At the same time, different beams of IMRT plans were compared to each other in respect to CI, HI and organs at risk (OAR) dose. BACKGROUND: Conventional early breast cancer treatment consists of lumpectomy followed by whole breast radiation therapy. CTT is a traditional method used for whole breast radiotherapy and includes standard wedged tangents (two opposed wedged tangential photon beams). The IMRT technique has been widely used for many treatment sites, allowing both improved sparing of normal tissues and more conformal dose distributions. IMRT is a new technique for whole breast radiotherapy. IMRT is used to improve conformity and homogeneity and used to reduce OAR doses. MATERIALS AND METHODS: Thirty patients with left-sided breast carcinoma were treated between 2005 and 2008 using 6, 18 or mixed 6/18 MV photons for primary breast irradiation following breast conserving surgery (BCS). The clinical target volume [CTV] was contoured as a target volume and the contralateral breast, ipsilateral lung, contralateral lung and heart tissues as organs at risk (OAR). IMRT with seven beams (IMRT7), nine beams (IMRT9) and 11 beams (IMRT11) plans were developed and compared with CTT and among each other. The conformity index (CI), homogeneity index (HI), and doses to OAR were compared to each other. RESULTS: ALL OF IMRT PLANS SIGNIFICANTLY IMPROVED CI (CTT: 0.76; IMRT7: 0.84; IMRT9: 0.84; IMRT11: 0.85), HI (CTT: 1.16; IMRT7: 1.12; IMRT9: 1.11; IMRT11: 1.11), volume of the ipsilateral lung receiving more than 20 Gy (>V20 Gy) (CTT: 14.6; IMRT7: 9.08; IMRT9: 8.10; IMRT11: 8.60), and volume of the heart receiving more than 30 Gy (>V30 Gy) (CTT: 6.7; IMRT7: 4.04; IMRT9: 2.80; IMRT11: 2.98) compared to CTT. All IMRT plans were found to significantly decrease >V20 Gy and >V30 Gy volumes compared to conformal plans. But IMRT plans increased the volume of OAR receiving low dose radiotherapy: volume of contralateral lung receiving 5 and 10 Gy (CTT: 0.0-0.0; IMRT7: 19.0-0.7; IMRT9: 17.2-0.66; IMRT11: 18.7-0.58, respectively) and volume of contralateral breast receiving 10 Gy (CTT: 0.03; IMRT7: 0.38; IMRT9: 0.60; IMRT11: 0.68). The differences among IMRT plans with increased number of beams were not statistically significant. CONCLUSION: IMRT significantly improved conformity and homogeneity index for plans. Heart and lung volumes receiving high doses were decreased, but OAR receiving low doses was increased.

Intraoperative Radiotherapy Is Not a Better Alternative to Whole Breast Radiotherapy as a Therapeutic Option for Early-Stage Breast Cancer.

OBJECTIVE: Intraoperative radiotherapy (IORT) in early-stage breast cancer has been studied over the years. However, it has not been demonstrated whether IORT is more suitable as a therapeutic option for early-stage breast cancer than whole breast radiotherapy (WBRT). Therefore, we performed a meta-analysis to compare the efficacy and safety of IORT to those of WBRT as therapeutic options for early-stage breast cancer patients receiving breast-conserving surgery (INPLASY2020120008). METHODS: PubMed, Embase, and Cochrane Library databases were searched from inception to October 2021. Computerized and manual searches were adopted to identify eligible randomized control trials from online databases. Risk ratio (RR) and 95% confidence intervals (CI) were calculated by random-effect models to assess the relative risk. Potential publication bias was quantified by Begg's and Egger's tests. RESULTS: Based on our inclusion criteria, 10 randomized control trials involving 5,698 patients were included in this meta-analysis. This meta-analysis showed that the IORT group was associated with a higher local recurrence risk (RR = 2.111, 95% CI, 1.130-3.943, p = 0.0191), especially in the long-term follow-up subgroup or published after 2020 subgroup or Caucasian subgroup (RR = 2.404, 95% CI, 1.183-4.885, p = 0.0154). Subgroup analysis showed that the IORT group had a higher recurrence risk than the WBRT group in the polycentric randomized controlled trial subgroup (RR = 1.213, 95% CI, 1.030-1.428, p = 0.0204). Pooled analysis showed that there was no statistically significant difference in overall survival, recurrence-free survival, distant metastasis-free survival, and cancer-specific survival between IORT and WBRT groups. Additionally, the risk of skin toxicity was reduced, but the incidences of fat toxicity, edema, and scar calcification were significantly increased in the patients who underwent IORT in comparison to those who underwent WBRT. CONCLUSION: This meta-analysis revealed that IORT was not a better alternative to WBRT. More large-scale and well-designed clinical trials with longer follow-up periods are encouraged to further investigate the value of IORT. SYSTEMATIC REVIEW REGISTRATION: https://inplasy.com/inplasy-2020-12-0008/.

State of the art in breast intraoperative electron radiation therapy after intraoperative ultrasound introduction.

BACKGROUND: Breast intraoperative electron radiation therapy (B-IOERT) can be used in clinical practice both as elective irradiation (partial breast irradiation - APBI) in low risk breast cancer patients, and as an anticipated boost. The procedure generally includes the use of a shielding disk between the residual breast and the pectoralis fascia for the protection of the tissues underneath the target volume. The aim of the study was to evaluate the role of intraoperative ultrasound (IOUS) in improving the quality of B-IOERT. PATIENTS AND METHODS: B-IOERT was introduced in Trieste in 2012 and its technique was improved in 2014 with IOUS. Both, needle and IOUS were used to measure target thickness and the latter was used even to check the correct position of the shielding disk. The primary endpoint of the study was the evaluation of the effectiveness of IOUS in reducing the risk of a disk misalignment related to B-IOERT and the secondary endpoint was the analysis of acute and late toxicity, by comparing two groups of patients treated with IOERT as a boost, either measured with IOUS and needle (Group 1) or with needle alone (Group 2). Acute and late toxicity were evaluated by validated scoring systems. RESULTS: From the institutional patients who were treated between June 2012 and October 2019, 109 were eligible for this study (corresponding to 110 cases, as one patients underwent bilateral conservative surgery and bilateral B-IOERT). Of these, 38 were allocated to group 1 and 72 to group 2. The target thickness measured with the IOUS probe and with the needle were similar (mean difference of 0.1 mm, p = 0.38). The percentage of patients in which the shield was perfectly aligned after IOUS introduction increased from 23% to more than 70%. Moreover, patients treated after IOUS guidance had less acute toxicity (36.8% vs. 48.6%, p = 0.33) from radiation therapy, which reached no statistical significance. Late toxicity turned out to be similar regardless of the use of IOUS guidance: 39.5% vs. 37.5% (p = 0.99). CONCLUSIONS: IOUS showed to be accurate in measuring the target depth and decrease the misalignment between collimator and disk. Furthermore there was an absolute decrease in acute toxicity, even though not statistically significant, in the group of women who underwent B-IOERT with IOUS guidance.

Dosimetric Comparison of Whole Breast Radiotherapy Using Field-in-Field and Volumetric Modulated Arc Therapy Techniques in Left-Sided Breast Cancer Patients.

Introduction The radiotherapy of left-sided breast cancers is challenging because of neighboring critical organs, posing an increased risk of complications. Various radiation delivery techniques have been used to deliver the desired dose of radiation to the target area while keeping the doses to nearby structures within constraints. The main aim of this study is to quantify doses delivered to the organs at risk (OARs) including heart, left lung, spinal cord, and contralateral breast, and to the planning target volume (PTV) using Field-in-Field (FIF) and Volumetric Modulated Arc Therapy (VMAT). Patients and methods A retrospective review of 15 left-sided breast cancer patients was done. All the patients underwent breast-conserving surgery and adjuvant radiation. For every patient, two different radiation treatment plans were formulated and compared for the PTV coverage and doses to OARs, including heart, ipsilateral lung, spinal cord, and contralateral breast. The radiation treatment techniques utilized for this purpose were FIF and VMAT. The homogeneity index (HI), and conformity index (CI) required for the treatment planning were also calculated. Data was analyzed using Statistical Package for the Social Sciences (IBM Corp., Armonk, USA). An Independent T-test was used for statistical analysis. Results The mean age was 41 years and the majority of them were stage II. Total nine patients were given 4005centi Gray (cGy) in 15 fractions (fr) followed by 10Gy boost, hence receiving a total dose of 5005cGy in 20fr. While remaining six patients were given a total dose 4005cGy in 15fr without any boost. All patients were hypofractionated and the dose was delivered at a rate of 267cGy per fr. The FIF technique utilized in breast cancer radiation significantly reduced the mean doses to OARs: mean heart dose (3.81cGy), ipsilateral lung dose (V16- 15cGy), mean contralateral breast dose (0.03cGy), and maximum spinal cord dose (0.18cGy); as compared to VMAT technique which delivered comparatively higher doses: mean heart dose (8.85cGy), ipsilateral lung dose (V16- 19.82cGy), mean contralateral breast dose (4.59cGy), and maximum spinal cord dose (7.14cGy). There was a significant mean difference between doses of OARs and all p-values were statistically significant (p<0.005). Moreover, the FIF technique also improves the dose distribution of PTV in terms of dose homogeneity. However, the conformity index is more enhanced with VMAT as opposed to FIF. Conclusion The FIF technique is more advantageous than the VMAT planning technique because it provides better dose distribution in terms of PTV coverage and significantly lower doses to OARs in radiotherapy to left-sided breast cancer.

Impact of molecular subtype on 1325 early-stage breast cancer patients homogeneously treated with hypofractionated radiotherapy without boost: Should the indications for radiotherapy be more personalized?

AIM: We report molecular subtype impact on 1325 early breast cancer (BCa) patients treated with whole breast hypofractionated (WBH) adjuvant forward-planned intensity modulated radiotherapy (F-IMRT) without boost. METHODS AND MATERIALS: From 02/2009-05/2017 1325 patients with pTis-pT3, pNx-N1aM0 BCa who underwent breast conservation surgery were treated with WBHF-IMRT in our institute, to a total dose of 40 Gy/15 fractions, without boost. Median age: 62 (interquartile range-IQR-:51.14-70.53) years. HISTOLOGY: 8% in situ carcinoma (ISC), 92% invasive tumors. Molecular subtypes (invasive tumors): 49.9% Luminal A, 33.1% Luminal B Her2 negative (-), 6.2% Luminal B Her2 positive (+), 3.6% Hormone Receptor (HR)- Her2+, 7.1% Triple negative (TNBC), and 0.2% HR+. Chemotherapy (CT) was prescribed in 28% of patients, hormonal therapy in 80.3%, monoclonal antibodies (MAb) in 86.8% of Luminal B Her2+ and 97.7% of HR- Her2+ patients. RESULTS: Median follow up was 72.43 (IQR: 44.63-104.13) months. The 5-year Kaplan-Meier estimates of local relapse-free survival (LRFS) was 97.8%, regional-(RRFS) 98.6%, loco-regional- (LRRFS) 96.9%, distant- (DRFS) 96.6%, disease-free survival (DFS) 94.8% and overall survival (OS) 95.5%. Considering molecular subtypes, 5-year LRFS was: 99.8% for Luminal A, 96.7% for Luminal B Her2-, 94.1% for Luminal B Her2+, 87.9% for HR- Her2+, 95.1% for TNBC and 99.1% for in situ carcinoma. CONCLUSION: While the overall estimated probability of LR within 5 years after WBHF-IMRT without boost is good (2.2%), molecular subtypes have a strong impact, despite MAb therapy in Her2+ patients, and CT for TNBC patients, and could be used as a parameter in deciding the boost prescription.

Partial-breast irradiation versus whole-breast radiotherapy for early breast cancer: A systematic review and update meta-analysis.

PURPOSE: The purpose of this study was to compare the treatment outcomes of partial-breast irradiation (PBI) versus whole-breast radiotherapy (WBRT) in early breast cancer. METHODS AND MATERIALS: Eligible randomized clinical trials were identified on Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through December 2019. A meta-analysis for local recurrence (LR), overall mortality (OM), and non-breast cancer mortality (NBCM) was conducted. When possible, the outcomes were calculated for 5, 7, and 10 years of followup. A subgroup analysis by PBI technique (brachytherapy [BT], external beam radiotherapy [EBRT], intraoperative radiotherapy [IORT], and mixed) was performed. A p value < 0.05 was considered significant. RESULTS: Eleven randomized clinical trials with a total of 14,436 patients (7186 PBI vs. 7250 WBRT) were included in the meta-analysis. The odds ratio (OR) for LR in 5 y was 1.46 (95% CI 1.15-2, p = 0.024) for PBI. In the subgroup analysis, no significant difference for LR was observed between PBI and WBRT using BT (p = 0.51), EBRT (p = 0.25), or mixed techniques (p = 0.89). The only subgroup with statistical difference was IORT 3.1 (95% CI 1.2-7.6, p = 0.014). No significant difference in LR was observed with 7 and 10 years among the groups. The OM had no difference at 5, 7, and 10 years of followup for any subgroup. A nonsignificant difference was observed comparing PBI with WBRT for NBCM OR = 1.24 (95% CI 0.98-1.57, p = 0.07). The rates of cardiac death, contralateral breast cancer, and development of second tumor were not significant. CONCLUSIONS: The LR with PBI is low and similar to WBRT in selected early breast cancer with a longer followup. The subgroup analysis detected a significant difference for LR associated with IORT and no significant difference for BT and EBRT. Our results confirm a nonsignificant difference for OM and NBCM between PBI and WBRT.

Fatigue following radiotherapy of low-risk early breast cancer - a randomized controlled trial of intraoperative electron radiotherapy versus standard hypofractionated whole-breast radiotherapy: the COSMOPOLITAN trial (NCT03838419).

BACKGROUND: Fatigue is one of the most common and distressing side-effects of breast cancer radiotherapy. According to current guidelines, accelerated partial breast irradiation (APBI) may be considered as an alternative treatment option for women with early-stage low-risk breast cancer. One method for APBI is single-dose intraoperative radiotherapy (IORT) applied directly to the tumor bed during breast conserving surgery (BCS). The COSMOPOLITAN trial therefore aims to analyze the intensity of fatigue following single-shot IORT with electrons (IOERT) compared to conventional hypofractionated whole breast irradiation (WBI) in low risk early breast cancer patients. METHODS: This trial is conducted as a multicenter, prospective, randomized, two-arm phase II study comparing the intensity of fatigue in early-stage breast cancer (cT1cN0cM0, tumor size < 2,5 cm, ER pos. Her2neu neg., age > 50 years) treated either with WBI or APBI after BCS. Secondary outcomes investigated are tumor control, overall survival (OS), disease-free survival (DFS), acute and chronic toxicity, quality of life (QoL) and cosmesis. A total of 202 patients will be randomized into two arms: Patients in arm A will receive WBI (40.05 Gy, 15 fractions) after surgical resection, while patients in arm B will receive IOERT (21 Gy to the 90%-isodose) during BCS. Fatigue will be assessed 12 weeks post surgery with the help of the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale. DISCUSSION: The present trial aims to evaluate treatment response to compare single-shot intraoperative electron APBI to conventional WBI following BCS in early-stage low risk breast cancer patients. Fatigue is selected as the primary, patient-reported endpoint due its major clinical relevance. TRIAL REGISTRATION: The study is prospectively registered on February 12th, 2019: Clinicaltrials.gov, NCT03838419. "Intraoperative Electron Radiotherapy for Low-risk Early Breast Cancer (COSMOPOLITAN)". STUDY STATUS: Ongoing study. Start of recruitment was December 2019.