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Objectives The efficacy of radiotherapy for breast cancer has greatly improved owing to better irradiation methods. Radiotherapy aims to deliver therapeutic doses to predetermined target volumes while sparing surrounding healthy tissues. However, there are few reports on radiation exposure to eye lenses, and the recommended exposure limits to ocular lens have been substantially reduced in recent years. This study aimed to investigate the amount of radiation exposure to eye lenses using optically stimulated luminescence dosimeters (OSLDs) and determine whether wearing special protective devices to protect the eyes, as an organ at risk, during whole breast irradiation, is necessary. Methods This experiment used OSLDs on water‐equivalent phantom to measure the change in scattered radiation dose due to the difference of irradiation field while using 4‐ and 6‐MV photons of TrueBeam linear accelerator. Using a total treatment dose of 50 Gy, a target was positioned to approximate the breast, and a plan was formulated to deliver 2 Gy per treatment by tangential irradiation. The mean (SD) irradiation dose at the lens position outside the irradiation field was reported. Results The scattered radiation dose outside the irradiation field was more affected by the irradiation field size than by the radiation energy. The out‐of‐field irradiation dose with a larger field of view was higher than that with a smaller field of view. The use of 0.07‐ and 0.83‐mm‐thick lead shield protective glasses reduced the radiation dose by 56.1% (P

To review postlumpectomy whole breast irradiation (WBI) in early-stage breast cancer with regard to the use of hypofractionation and a tumor bed boost. Hypofractionation is currently standard practice for most cases of postlumpectomy WBI. A boost is recommended for women at increased risk for local recurrence due to clinical or pathologic risk factors. A sequential boost is currently standard practice for WBI with either conventional or hypofractionated radiation. Phase I–II trials of hypofractionation and concurrent boost have shown comparably low risks for local recurrence and acute and late toxicity without adding additional treatment days to WBI. Postlumpectomy WBI with hypofractionation and concurrent boost is a promising method of gaining the local control benefit of a tumor bed boost but maintaining the shorter treatment length, lower cost, and convenience of hypofractionation. Phase III trials are pending that may make this approach more widely accepted practice.

Purpose of Review Accelerated partial breast irradiation (APBI) is an alternative approach to breast conserving therapy (BCT) where radiation (RT) is delivered over a shorter period of time compared with whole breast irradiation (WBI), resulting in improved patient convenience and cost savings. APBI can be delivered using brachytherapy, intraoperative RT, or conformal external beam radiation therapy (EBRT) techniques. In this review, the authors appraise the latest modern randomized controlled trials (RCTs) of APBI and discuss the application of the data to clinical practice. Recent Findings The OCOG-RAPID and NSABP B-39/RTOG 0413 trials recently reported long-term outcomes of APBI. The OCOG-RAPID trial delivered 38.5 Gy/10 fractions twice daily (at least 6 h apart using EBRT) or WBI and demonstrated non-inferiority of APBI compared with WBI (8-year cumulative rate of ipsilateral breast tumor recurrence (IBTR) was 3% after APBI or 2.8% after WBI, HR 1.27, 90%CI: 0.84–1.91). While acute toxicity was reduced, late toxicity and breast cosmesis were worse with APBI. The NSABP B-39 trial included higher risk patients and was unable to demonstrate equivalence between APBI (38.5 Gy/10 fractions delivered twice daily using EBRT or brachytherapy techniques) and WBI. However, 10-year IBTR rates were low: 4.6% vs. 3.9%, respectively, HR 1.22, 90%CI: 0.94–1.58. The University of Florence demonstrated low rates of local recurrence at 10 years and overall excellent breast cosmetic outcomes when APBI was delivered using EBRT to a dose of 30 Gy/5 fractions delivered on non-consecutive days. Summary Recent RCTs of APBI have shed light on important factors for the integration of APBI into clinical practice, including patient selection and treatment delivery. APBI should be limited to patients with low-risk ductal carcinoma in situ or early stage (T1) invasive ductal cancer with clear margins of excision, estrogen receptor positivity, and node negative disease. Ongoing research should focus on the optimal dose/fractionation for delivery of EBRT-based APBI.

BACKGROUND: Whole breast irradiation after breast-conserving surgery (BCS) with an external beam boost of 10–16 Gy is currently the standard treatment in breast cancer. Various modalities have been used for tumor bed boost irradiation. This study aimed to evaluate the local recurrence rate, overall survival rate (OSR), toxicity and cosmetic outcome of intraoperative radiotherapy (IORT) as a boost followed by whole breast irradiation in patients who received BCS. METHODS: This is a retrospective study. Between December 2009 and March 2017, 81 patients who underwent BCS with IORT as a boost were enrolled in this study. For IORT, a single dose of 20 Gy was delivered using a 30–50 kV photon beam, intraoperatively. All patients received whole breast radiation therapy (WBRT) of 42.5–50 Gy over 4–5 weeks. The primary endpoint was a 3-year local recurrence rate. Secondary endpoints included the OSR, toxicity and cosmetic outcome at 6 months after radiation treatment. RESULTS: At a median follow-up of 43 months, ipsilateral local recurrence was observed in one of the 81 patients (1.2%) which occurred in the same quadrant of the breast index. The 3-year OSR was 89.8%. Treatment was well-tolerated with no grade 3–4 acute and late toxicity, and 87% of patients were recorded as excellent–good cosmesis. CONCLUSIONS: The use of BCS with IORT as a boost resulted in a low local recurrence rate and excellent cosmetic outcome in early breast cancer. Thus, IORT as a boost could be considered as an alternative to an external beam boost. Prospective studies are needed to confirm this data.

Purpose: This planning study compared the various dosimetric parameters of different types of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) techniques for left-sided breast cancer radiotherapy. Materials and Methods: Treatment of 22 left-sided breast cases was planned using two IMRT and VMAT techniques for the prescription of 40 Gy in 15 fractions. For tangential IMRT (Tan_IMRT), five beams were placed as conventional tangential beams. For equally spaced IMRT (Equi_IMRT), six beams were placed equidistantly at 40° interval from 300° to 140°. For tangential VMAT (Tan_VMAT), two arcs were used with the avoidance sector in such a way that the beam covered like tangential fields. For full-arc VMAT (Full_VMAT), similar arcs as Tan_VMAT were used, without avoidance sector. All treatment plans were generated using Eclipse planning system for TrueBeam STx linear accelerator. For planning target volume (PTV), dose parameters including D95%, D99%, V105% homogeneity index (HI), and conformity index (CI) were analyzed. Different dose parameters for the left lung, heart, left anterior descending artery (LAD), right lung, and right breast were also analyzed. In addition, low-dose spillage in the normal tissues and the number of monitor units (MUs) required for the treatment were compared. Results: IMRT technique exhibited superior D95% and D99% for PTV compared with VMAT techniques. VMAT plans provided more V105% (6%) compared with that of IMRT plans (approximately 1%). HI was better in IMRT plans (Tan_IMRT, 0.085 ± 0.015; Equi_IMRT, 0.094 ± 0.011) than in VMAT plans. CI was better in VMAT plans. The mean lung dose (7.7 Gy ± 1.788 Gy) and V5Gy (34.99% ± 6.799%) were better achieved in Tan_IMRT plan than other plans. Right lung, heart, and right breast sparing were better achieved in Tan_IMRT plan. Moreover, low-dose spillage was very less in the Tan_IMRT compared with all other techniques. Conclusion: Dosimetric comparison in this study showed that tangential IMRT technique is superior in terms of target coverage, sparing of lung, heart, and right breast, and low-dose spillage control in the left-sided breast-only radiotherapy.

Purpose Intraoperative radiation therapy (IORT), a form of accelerated partial breast irradiation (APBI), is an appealing alternative to postoperative whole breast irradiation for early-stage breast cancer. The purpose of this study was to examine the toxicity and cosmetic outcomes of patients treated with a novel form of breast IORT (precision breast IORT; PB-IORT), that delivers a targeted, higher dose of radiation than conventional IORT. Methods and Materials The first 204 patients treated with PB-IORT in a Phase II clinical trial (NCT02400658) with 12 months of followup were included. Trial inclusion criteria were age ≥45 years, invasive or in situ breast cancer, tumor size ≤3 cm, and node negative. Toxicity and cosmetic scoring were performed at 6 and 12 months. Results 98 patients (48%; 95% CI, 41–55%) experienced toxicity. Seven Grade 3 toxicities occurred (3.4%; 95% CI, 1.4–6.9%). Most patients (95%) had excellent or good cosmetic outcomes (95% CI, 91–98%) at 12 months. Most patients (94%) had little or no pigmentation change (95% CI, 90–97%), 88% little to no size change (95% CI, 82–92%), and 87% experienced minimal shape change (95% CI, 82–92%). Conclusions Overall, Grade 3+ toxicity was rare and cosmetic outcomes were excellent. Severe toxicity with PB-IORT is similar to that reported in the TARGIT trial (3.3% rate of major toxicity) but lower than APBI (NSABP-39, 10.1% Grade 3/4 toxicities). We propose that the toxicity of PB-IORT compared with TARGIT and NSABP-39 is related to the radiation dose and delivery schedule. PB-IORT offers low-toxicity and good cosmetic outcomes when compared with other forms of APBI.

The aim of this study was to propose a methodology for the assessment of non-inferiority with meta-analysis. Assessment of hypofractionated RT in prostate and breast cancers is used as an illustrative example. Non-inferiority assessment of an experimental treatment versus an active comparator should rely on two elements: (1) an estimation of experimental treatment’s effect versus the active comparator based on a meta-analysis of randomized controlled trials and (2) the value of an objective non-inferiority margin. This margin can be defined using the reported effect of active comparator and the percentage of the active comparator’s effect that is desired to be preserved. Non-inferiority can then be assessed by comparing the upper bound of the 95% confidence interval of experimental treatment’s effect to the value of the objective non-inferiority margin. Application to hypofractionated RT in breast cancer showed that hypofractionated whole breast irradiation (HWBI) appeared to be non-inferior to conventionally fractionated RT for local recurrence. This was not the case for accelerated partial breast irradiation (APBI). Concerning overall survival, non-inferiority could not be claimed for either HWBI or APBI. For prostate cancer, the lack of demonstrated significant superiority of conventional RT versus no RT precluded any conclusion regarding non-inferiority of hypofractionated RT.

Whole breast irradiation after breast conserving surgery (BCS) is the standard treatment for early stage breast cancer. For early-stage breast cancer, breast-conserving surgery and subsequent postoperative radiotherapy are as effective as mastectomy. An early stage 10 breast cancer patient admitted to the Radiation Oncology Clinic of Sisli Hamidiye Etfal Training and Research Hospital was included in the study. The study is a retrospective study and patients were not treated with the plans and techniques used in the studies. In the study, the planning target volume (PTV) and the organs at risk (OAR) planned with Sequential Intensity Modulated Radiotherapy (IMRT) and Simultaneous Integrated Supplement (Boost) Intensity Modulated Radiotherapy (SIB IMRT) techniques in patients who have undergone breast conserving surgery due to breast cancer. It is aimed to be compared dosimetrically. For the study, patients with consecutive IMRT were given 50 Gy / 25 fraction to the whole breast and 10 Gy / 5 fraction to the boost area, while patients with SIB IMRT were given a total of 50.4 Gy / 28 fractions to the entire breast, while additional dose to the boost volume was given 60 Gy / 28 fraction dose. Ipsilateral lung, heart, the minimum and maximum doses of the PTV breast and PTV boost areas and the homogeneity index (HI), conformity index (CI) values were matched with the help of the t - test minitab program. SIB IMRT technique and Sequential IMRT technique the ipsilateral lung; When the average doses of V5 value for 10 patients are compared, the results are not statistically significant, while the V20 value is statistically significant when the average dose values for 10 patients are compared, it has been demonstrated that SIB IMRT technique can be performed with a lower dose in the ipsilateral lung V20. When the heart average and heart V20 values are compared for the two techniques, the SIB IMRT technique was not statistically significant, and it has no superiority over the Sequential IMRT technique. While dose homogeneity was better with SIB IMRT in whole breasts, there was no difference in boost area homogeneity and whole breast conformity index SIB IMRT technique for decreasing excess normal tissue volumes irradiated, shortening the treatment process, dose reduction in organs at risk, reducing the dose per fraction for the breast and increasing the dose per fraction to the boost area due to the low incidence of acute skin toxicity, standard use in breast protector RT it can be recommended for.

Extending the superior border of the breast tangent fields to include the low axilla is a technique employed to target the axillary lymph node (LN) without adding additional fields. This technique, commonly referred to as high tangents, is typically done in the supine position. The feasibility of delivering high tangents in the prone position has never been reported. Patients from 2012 to 2018 at a single institution who were prescribed treatment with high tangents using two tangentially opposed beams in the prone position were identified. The levels I–III axillary LNs were retrospectively contoured. The dose delivered to the LN, breast, and organs at risk was calculated using the original treatment plan. For LN, coverage was defined as > 90% of the prescribed dose. Forty-one patients treated with high tangents were identified. The median age was 62. Most patients underwent sentinel LN biopsy (88%), of which 59% had macroscopic disease and 30% had micrometastatic disease. Four patients had no axillary staging. Most patients (76%) were treated with hypofractionated radiation. The median distance from the superior border of the anterior oblique field to the humeral head was 0.6 cm (range: 0–1.5 cm). The mean coverage of the level I and level II axilla was 88.7% and 40.0% respectively. Axillary level I coverage for distance from the humeral head 1 cm was 76.4% (p = 0.017). This series demonstrates the feasibility of high tangents in the prone position, offering good coverage of level I LN, particularly with

To assess the acute toxicity and quality of life (QOL) of hypofractionation compared with conventional fractionation for whole breast irradiation (WBI) after breast-conserving surgery.Women with node-negative breast cancer who had undergone breast-conserving surgery with clear margins were randomly assigned to conventional WBI of 5000 cGy in 25 fractions over 35 days or hypofractionated WBI of 4256 cGy in 16 fractions over 22 days. Acute skin toxicity and QOL were assessed at baseline and 2, 4, 6, and 8 weeks from the start of treatment for a subgroup of patients. QOL was assessed at baseline and 4 weeks posttreatment for all patients. In the acute toxicity substudy, repeated measures modeling was used to investigate treatment by time interactions over the 8-week period for acute toxicity and QOL mean change score. QOL mean change score from baseline to 4 weeks posttreatment was compared for all patients.In the acute toxicity substudy, 161 patients participated. In the main trial, 1152 patients participated. Acute skin toxicity was initially similar between groups but was less with hypofractionation compared with conventional fractionation toward the end of the 8-week period (P.001). QOL at 6 weeks from the start of treatment was improved with hypofractionation for the skin side effects, breast side effects, fatigue, attractiveness, and convenience domains (all P.05). In the main trial, hypofractionation resulted in improved overall QOL and QOL attributed to skin side effects, breast side effects, and attractiveness (all P.01).Hypofractionated WBI compared with conventional WBI resulted in less acute toxicity and improved QOL. This further supports the benefits of hypofractionation.

In this prospective longitudinal study, Coronary Artery Calcium (CAC) scores determined before the start of whole breast irradiation were compared with those determined 7 years afterwards. The aim was to examine whether the use of a breath-hold (BH) technique is associated with less increase of CAC scores.Changes in CAC scores were analysed in 87 breast cancer patients. The results of the following groups were compared: patients receiving right (R) or left-sided radiotherapy using free breathing (L-FB) with those receiving left-sided radiotherapy with BH (L-BH). We compared the changes of CAC scores between these groups over time, testing the hypothesis that a significantly reduced increase of calcium scores is observed when using BH.For L-BH cases, when compared with L-FB cases, for overall as well as for Left Anterior Descending coronary artery (LAD) CAC scores, we noted significantly less increased CAC scores (p 0.01). This effect of BH was even more striking in the group with CAC scores0 at baseline. The attenuated increase over time of CAC scores in the L-BH group was robust to correction for age and statin use (p 0.05).After a median follow-up of 7.4 years, we found significantly less increased CAC scores when using BH. This is a relevant finding since higher levels of CAC scores are associated with higher probabilities of coronary artery events. Moreover, it underlines the rationale for the use of BH in left-sided whole breast irradiation.

The role of radiation therapy in the management of breast cancer continues to evolve. For patients with early stage breast cancer, hypofractionated whole breast irradiation following breast conserving surgery now represents the standard of care based on randomized data with long-term efficacy and toxicity outcomes. Partial breast irradiation has been found, in several randomized trials, to be effective and appropriate in selected patients with the potential to reduce toxicities as compared to whole breast irradiation. The study of tumor biology and genetics and its role in radiation therapy decision making continues to grow and the advances may help identify patients where radiation therapy can be safely omitted, with future studies looking at de-intensification approaches. Recent randomized data has demonstrated a growing role for regional nodal irradiation in patients with more advanced disease, with future studies looking to identify whether nodal radiation is indicated following neoadjuvant chemotherapy or with certain favorable tumor biologies. While postmastectomy radiation therapy represents a standard approach for patients with locally advanced breast cancer, new data supports the role of hypofractionated regimens as well as its use in patients previously considered lower risk with unfavorable tumor biology. Oligometastatic disease represents a new area of study in breast cancer with prospective trials underway and current data supporting consideration of techniques such as stereotactic body radiation therapy in appropriately selected patients.

Purpose Radiation therapy (RT) after breast-conserving surgery reduces locoregional recurrences and improves survival but may cause late side effects. The main purpose of this paper was to investigate long-term side effects after whole breast RT in a randomized clinical trial initiated in 1991 and to report dose-volume data based on individual 3-dimensional treatment plans for organs at risk. Methods and Materials The trial included 1187 patients with T1-2 N0 breast cancer randomized to postoperative tangential whole breast RT or no further treatment. The prescription dose to the clinical target volume was 48 to 54 Gy. We present 20-year follow-up on survival, cause of death, morbidity, and later malignancies. For a cohort of patients (n = 157) with accessible computed tomography–based 3-dimensional treatment plans in Dicom-RT format, dose-volume descriptors for organs at risk were derived. In addition, these were compared with dose-volume data for a cohort of patients treated with contemporary RT techniques. Results The cumulative incidence of cardiac mortality was 12.4% in the control group and 13.0% in the RT group (P = .8). There was an increase in stroke mortality: 3.4% in the control group versus 6.7% in the RT group (P = .018). Incidences of contralateral breast cancer and lung cancer were similar between groups. The median Dmean (range) heart dose for left-sided treatments was 3.0 Gy (1.1-8.1), and the corresponding value for patients treated in 2017 was 1.5 Gy (0.4-6.0). Conclusions In this trial, serious late side effects of whole breast RT were limited and less than previously reported in large meta-analyses. We observed no increase in cardiac mortality in irradiated patients. Doses to the heart were a median Dmean of 3.0 Gy for left-sided RT. The observed increase in stroke mortality may partly be secondary to cardiac side effects, complications to anticoagulant treatment, or to chance, rather than a direct side effect of tangential whole breast irradiation.

Breast cancer (Ca) comprises the most common cancer in females and constitutes a leading cause of cancer related deaths around the globe.

Although phase III trials have been published comparing whole breast irradiation (WBI) with accelerated partial breast irradiation (APBI) using intraoperative radiotherapy (IORT), long-term follow-up results are lacking. We report the 10-year follow-up results of a prospective phase I/II clinical trial of IORT. The inclusion criteria were as follows: (i) tumor size 50 years, (iv) negative margins after resection and (v) sentinel lymph node-negative disease. A single dose of IORT (19–21 Gy) was delivered to the tumor bed in the operation room just after wide local excision of the primary breast cancer using a 6–12 MeV electron beam. Local recurrence was defined as recurrence or new disease within the treated breast and was evaluated annually using mammography and ultrasonography. A total of 32 patients were eligible for evaluation. The median patient age was 65 years and the median follow-up time was 10 years. Two patients experienced local recurrence just under the nipple, out of the irradiated field, after 8 years of follow-up. Three patients had contralateral breast cancer and one patient experienced bone metastasis after 10 years of follow-up. No patient experienced in-field recurrence nor breast cancer death. Eight patients had hypertrophic scarring at the last follow-up. There were no lung or heart adverse effects. This is the first report of 10-year follow-up results of IORT as APBI. The findings suggest that breast cancer with extended intraductal components should be treated with great caution.

Hypofractionated whole breast irradiation (HWBI) is the current standard of treatment after breast conservative surgery (BCS). Intraoperative radiotherapy (IORT) must be associated to WBI in patients showing high-risk factors of local recurrence in the definitive pathology report. The aim of this trial was to evaluate, for the first time, the acute toxicity and cosmesis of HWBI after photon-IORT. Twenty-six luminal breast cancer patients treated by BCS and IORT(20 Gy) were included between February and December 2019, in this prospective trial, of adjuvant HWBI (40.5 Gy/2.67 Gy/15 fractions). Acute toxicity (CTCAEv5.0) and cosmesis (Harvard scale), were assessed 3 months after treatment. All patients completed their treatment without interruptions. All cases were evaluable 3 months after treatment showing no toxicity ≥ G3 and excellent/good cosmesis assessment in 88% of the patients. HWBI seems to have similar acute toxicity and cosmesis results than conventionally fractionated WBI in combination to photon-IORT after BCS.

Two prospective randomized trials, TARGIT-A and ELIOT, have shown intraoperative radiation (IORT) to be safe and well-tolerated in low-risk patients. Electronic IORT with the Xoft Axxent system has few long-term reported results. A total of 100 patients (101 tumors) were treated with partial mastectomy and intraoperative brachytherapy. Electronic brachytherapy via IORT was utilized to deliver 20 Gy to the balloon surface in a single fraction prior to completion of surgery. Necessity of additional intervention with surgery or radiation was noted, as was the presence of clinical seroma and tumor recurrence. Patients were followed at regular intervals for at least 5 years. Patients ranged in age from 41 to 83, with a median age of 66. Out of the 101 tumors treated, T-staging consisted of 28.7% Tis, 2.0% T1mi, 11.9% T1a, 23.8% T1b, 30.7% T1c, and 3.0% T2. At a median follow up of 3.8 years, there have been two recurrences. Eighteen patients required additional surgery or radiation. Patients classified as “suitable” by the accelerated partial breast irradiation suitability criteria were less likely to require re-excision (suitable: 1.6%, cautionary: 22.6%, unsuitable: 87.5%, P

Radiation dermatitis represents one of the most frequent side effects in breast cancer patients undergoing adjuvant whole-breast irradiation (WBI). Whether hypofractionated WBI induces comparable or less acute radiation-induced skin reactions than conventional WBI is still not fully clarified, as randomized evidence and objective assessments are limited. The aim of this study was to objectively determine frequency and severity of acute radiation-induced skin reactions during hypofractionated vs. conventionally fractionated adjuvant WBI.In this randomized multicenter study, a total of 140 breast cancer patients underwent either hypofractionated or conventional WBI following breast-preserving surgery. Maximum radiation dermatitis severity was assessed at completion and during follow-up by physician-assessed CTCAE v4.03 and the patient-reported RISRAS scale. Additionally, photospectrometric skin readings were performed to objectify skin color differences between both treatment arms.Radiation dermatitis severity was significantly lower in patients receiving hypofractionation compared with conventional fractionation (mean 1.05 vs. 1.43, p = .024). Grade 0 radiation dermatitis occurred in 21.43% vs. 4.28%, grade ≥2 in 27.14% vs. 42.91% and grade ≥3 in 0% vs. 4.34% of patients following hypofractionated and conventional WBI, respectively. Objective photospectrometric measurements (n = 4200) showed both decreased erythema severity (p = .008) and hyperpigmentation (p = .002) in the hypofractionation arm. Patients allocated to hypofractionated WBI also reported less pain (p = .006), less hyperpigmentation (p = 0.001) and less limitations of day-to-day activities (p = 0.001).Physician and patient-assessed toxicity scorings as well as objective photospectrometric skin measurements revealed that hypofractionated WBI yielded lower rates and severity of acute radiation-induced skin toxicity.

Purpose: Our purpose was to use 3-dimensional (3D) surface photography to quantitatively measure breast cosmesis within the framework of a randomized clinical trial of conventionally fractionated (CF) and hypofractionated (HF) whole breast irradiation (WBI); to identify how 3D measurements are associated with patient- and physician-reported cosmesis; and to determine whether objective measures of breast symmetry varied by WBI treatment arm or transforming growth factor β 1 (TGFβ1) status. Methods and Materials: From 2011 to 2014, 287 women age ≥40 with ductal carcinoma in situ or early-stage invasive breast cancer were enrolled in a multicenter trial and randomized to HF-WBI or CF-WBI with a boost. Three-dimensional surface photography was performed at 3 years posttreatment. Patient-reported cosmetic outcomes were recorded with the Breast Cancer Treatment Outcome Scale. Physician-reported cosmetic outcomes were assessed by the Radiation Therapy Oncology Group scale. Volume ratios and 6 quantitative measures of breast symmetry, termed F1-6C, were calculated using the breast contour and fiducial points assessed on 3D surface images. Associations between all metrics, patient- and physician-reported cosmesis, treatment arm, and TGFβ1 genotype were performed using the Kruskal-Wallis test and multivariable logistic regression models. Results: Among 77 (39 CF-WBI and 38 HF-WBI) evaluable patients, both patient- and physician-reported cosmetic outcomes were significantly associated with the F1C vertical symmetry measure (both P < .05). Higher dichotomized F1C and volumetric symmetry measures were associated with improved patient- and physician-reported cosmesis on multivariable logistic regression (both P ≤ .05). There were no statistically significant differences in vertical symmetry or volume measures between treatment arms. Increased F6C horizontal symmetry was observed in the CF-WBI arm (P = .05). Patients with the TGFβ1 C-509T variant allele had lower F2C vertical symmetry measures (P = .02). Conclusions: Quantitative 3D image-derived measures revealed comparable cosmetic outcomes with HF-WBI compared with CF-WBI. Our findings suggest that 3D surface imaging may be a more sensitive method for measuring subtle cosmetic changes than global patient- or physician-reported assessments.

Introduction External beam partial breast irradiation (PBI) provides equal oncological outcomes compared to whole breast irradiation when applied to patients with low risk tumours. Recently, linacs with an integrated magnetic resonance image-guidance system have become clinically available. Here we report the first-in-human PBI performed at the 1.5 T MR-Linac, with a focus on clinical feasibility and investigation of the air electron stream effect (ESE) and the electron return effect (ERE) in the presence of the 1.5 T magnetic field, which might influence the dose on the chin (out-of-field dose, due to the ESE), the skin and the lung/chest wall interface (in-field dose, ERE). Methods A 59 years old patient affected by a 15 mm unifocal grade 1 carcinoma not special type of the right breast staged pT1c pN0 cM0 was planned and treated at Unity 1.5 T MR-Linac. To investigate the ERE and the ESE, an MR-Linac treatment plan was simulated without considering the 1.5 T B field using a research version of Monaco (V. 5.19.03). In vivo dosimetry was performed using Gafchromic® EBT3 films placed on top and underneath a 1 cm bolus which was placed on the patient’s chin. The plans with and without 1.5 T magnetic field were compared in terms of dose to the chin, to the skin and to the interface lung/chest wall. Finally, the dose on the chin measured with the in vivo dosimetry was compared with the dose calculated by Monaco. Results PBI using the 1.5 T MR-Linac was successfully performed with a 7 MV photon 7-beams IMRT step-and-shoot plan. The treatment was well tolerated, the patient developed a slight acute toxicity, i.e. breast skin erythema and breast oedema CTC V.4 grade 1. The plan with 1.5 T magnetic field documented a fractional dose of 0.17 Gy in the chin area (2.6 Gy in 15 fractions), which was reduced to 0.05 Gy (0.75 in 15 fractions) by the presence of 1 cm bolus. The simulated plan without magnetic field showed a dose reduced by 2.3 Gy in the chin area. With the in vivo dosimetry a fractional dose of, respectively, 0.12 Gy and 0.034 Gy on top and underneath the bolus were measured (1.8 and 0.51 Gy in 15 fractions). The plan with 1.5 T magnetic field showed a skin D2 of 40 Gy and a skin V35 of 40.2%, which were reduced to, respectively, 39.7 Gy and 24.9% in the simulation without magnetic field. At the interface lung/chest there were no differences in DVH statistics. Conclusion PBI with the 1.5 T MR-Linac was performed for the first time. ESE is accurately calculated by the treatment planning system, can be effectively reduced with a 1 cm bolus and is comparable to dose of cone beam-CT based position verification. The additional dose caused by ERE is not associated with an increased risk of acute toxicity.

Purpose To evaluate the necessity of regional nodal irradiation (RNI) for pT1-2N1 breast cancer patients treated with breast-conserving surgery and radiotherapy, we compared clinical outcomes of patients treated with and without RNI. Materials and methods We retrospectively analyzed the data of 214 pT1-2N1 breast cancer patients treated with breast-conserving surgery and whole breast irradiation from 2009-2016. There were 142 (66.4%), 51 (23.85%), and 21 (9.8%) patients with one, two, and three positive lymph nodes, respectively. Thirty-six patients (16.8%) underwent RNI. Adjuvant chemotherapy, endocrine therapy, and anti-HER2 therapy were given to 91.6%, 79.0%, and 15.0% patients, respectively. The most common chemotherapy regimen was anthracycline + cyclophosphamide, followed by taxane (76.5%). The median follow-up was 64 months (range, 6 to 147 months). Patients were propensity matched 1:2 into RNI and no-RNI groups. Results Two patients experienced locoregional recurrences simultaneously with distant metastases, ten patients developed distant metastases, and one patient died. Before matching, the 5-year actuarial locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) rates in the RNI and no-RNI groups were 100.0% and 99.4% (p = 0.629), 94.1% and 96.0% (p = 0.676), and 100.0% and 99.4% (p = 0.658), respectively. After matching, the 5-year LRC, DMFS, and OS were 98.3% and 100.0% (p = 0.455), 96.6% and 93.9% (p = 0.557), and 100.0% and 100.0% (p > 0.999) in the RNI and no-RNI groups, respectively. No clinicopathologic or treatment-related factors were significantly associated with LRC, DMFS, or OS. Conclusion Adding RNI did not show superior LRC, DMFS, or OS in pT1-2N1 breast cancer patients.

Adjuvant radiation therapy has been associated with improved local control following breast-conserving surgery. Traditionally, treatment has been delivered with whole breast irradiation over 3-6 weeks or partial breast irradiation over 1-3 weeks. However, intraoperative radiation therapy (IORT) has emerged as a technique that delivers a single dose of radiotherapy at the time of surgery for early-stage breast cancers. We report initial outcomes and acute toxicities with intraoperative radiation from a single institution. Patients with DCIS or Stage I-II breast cancer who underwent lumpectomy and sentinel lymph node biopsy (nodal sampling excluded in some cases) were included. All patients in this analysis were treated with IORT as at the time of surgery, 20 Gy in 1 fraction with 50 kV x-ray. Patients were treated at a single institution between 2011 and 2019. Follow-up was per standard institutional protocol. Two hundred and one patients were included in the analysis, with a median follow-up of 23 months (range: 0-73 months). Median age was 71 years old. Overall, 4 (2.0%) patients had DCIS, 186 (92.5%) patients had Stage 1 disease, and 11 patients had (5.5%) Stage 2 disease. All patients were estrogen receptor-positive, 175 (87.9%) progesterone receptor-positive, and 1 (0.5%) HER2 amplified. The crude rate of local recurrence was 2.0% (n = 4) and distant metastasis rate was 0.5% (n = 1). The rate of arm lymphedema was 0.5% (n = 1) and chronic telangiectasia rate was 1.1% (n = 2). Intraoperative radiation therapy, in a cohort of low-risk patients, demonstrated low rates of recurrence and reproducibility in a multi-disciplinary setting. Further follow-up, analysis of patient satisfaction and cosmesis, and comparison to whole breast irradiation and partial breast techniques is necessary in order to further validate these findings.

Highlights • Post-operative radiotherapy is standard after breast conservation in early breast cancer. • To de-escalate the treatment burden, indentifying a subset at very low risk of relapse is crucial. • Clinical and pathological factors are important, but can be integrated with genomic signatures. • Ongoing trials will provide evidence on patients at low risk for radiotherapy omission., Radiation therapy is a standard therapeutic option in the post-operative setting for early breast cancer patients after breast conserving surgery, providing a substantial benefit in reducing the risk of local relapse with a consequent survival gain. Nevertheless, the reduction in the burden related to treatment is becoming crucial in modern oncology for both local and systemic therapies and investigational efforts are being put forward by radiations oncologists to identify a subset of women at very low risk to be potentially omitted from post-operative irradiation after breast conservation. Clinical factors, classical pathological parameters and new predictive scores derived from gene expression and next generation sequencing techniques are being integrated in the quest toward a reliable low-risk profile for breast cancer patients. We herein provide a comprehensive overview on the topic.

To investigate long-term results of patients with hormonal receptor-positive breast cancer treated with breast-conserving surgery (BCS) and consecutive endocrine therapy (ET) with or without whole breast irradiation (WBI).Within the 8 A trial of the Austrian Breast and Colorectal Cancer Study Group, a total of 869 patients received ET after BCS which was randomly followed by WBI (n = 439, group 1) or observation (n = 430, group 2). WBI was applied up to a mean total dosage of 50 Gy (+/- 10 Gy boost) in conventional fractionation.After a median follow-up of 9.89 years, 10 in-breast recurrences (IBRs) were observed in group 1 and 31 in group 2, resulting in a 10-year local recurrence-free survival (LRFS) of 97.5% and 92.4%, respectively (p = 0.004). This translated into significantly higher rates for disease-free survival (DFS): 94.5% group 1 vs 88.4% group 2, p = 0.0156. For distant metastases-free survival (DMFS) and overall survival (OS), respective 10-year rates amounted 96.7% and 86.6% for group 1 versus 96.4% and 87.6%, for group 2 (ns). WBI (hazard ratio [HR]: 0.27, p 0.01) and tumour grading (HR: 3.76, p = 0.03) were found as significant predictors for IBR in multiple cox regression analysis.After a median follow-up of 10 years, WBI resulted in a better local control and DFS compared with ET alone. The omission of WBI and tumour grading, respectively, were the only negative predictors for LRFS.

Purpose: Partial Breast Irradiation (PBI) treats the tumor bed plus a margin in low risk early stage breast cancers, reducing exposure to organs at risk. Randomized trials have shown that PBI with external beam radiotherapy is non-inferior to whole breast irradiation in terms of local control with fewer late normal tissue adverse events. We aimed to determine the proportion of women with early stage breast cancer suitable for external beam PBI at our institution using adapted ASTRO guidelines for accelerated PBI whereby both clinical-pathological factors and visualization of the tumor bed/cavity on planning scans were determined to quantify PBI eligibility. Methods: Patients were identified retrospectively from January 1, 2013 to November 1, 2018 based on age (≥55), tumor size (≤2cm invasive, ≤2.5cm DCIS), nodal negativity and grade (1 or 2). Cases identified were unifocal, lymphovascular invasion negative, ER positive, HER2 negative, with margins ≥2mm (invasive) and ≥3mm (DCIS), no chemotherapy, non-lobular, no extensive intraductal component, no previous/ bilateral cancers and endocrine therapy optional. Planning scans were reviewed to assess for presence of surgical clips and assigned cavity visualization scores (CVS); CVS 1=cavity not visualized, CVS 2=cavity visualized with indistinct margins, CVS 3=cavity visualised with some distinct margins and heterogeneous appearance, CVS 4= cavity visualised with mostly distinct margins and mildly heterogeneous appearance, CVS 5= all cavity margins clearly defined and homogeneous appearance. These features were used to determine if cases were considered radiologically suitable for PBI. Results: Thirty-seven percent (1051/2824) of cases identified were deemed eligible based on age, grade and T1N0/Tis. Of the 1051, 306 (29%) met all the pathologic criteria; the main reasons for exclusion were previous breast cancer, lobular histology, or multifocality. Median age of eligible cases was 65 years (range 55-88 years). The majority (254) had invasive disease (T1mi: 6, T1a: 17, T1b: 98, T1c: 133); 52 had DCIS. There were 169 right-sided and 137 left-sided cases. Endocrine therapy was documented in 55% of cases. CVS (1-5) were: 11%, 22%, 30%, 29%, 8%. Overall, 66% (201/306) of cases were considered radiologically suitable for PBI (of the 201 cases, 97% had CVS ≥3). Seventy-two cases (72/306; 24%) had tumor bed clips, of which, 34 were considered suitable for PBI (91% CVS ≥3; 9% CVS 2). Conclusions: Overall, a low proportion of all patients were eligible for PBI based on clinical features, but two-thirds of eligible cases were suitable for PBI based on CVS score alone. In contrast, the suitability for PBI within the cohort with surgical clip placement was low. Visualization of the tumor bed is essential to safely deliver PBI and is guided by identification of the cavity seroma and/or surgical clips. Development of standard practice guidelines for surgical clip positioning to identify the tumor bed will potentially assist in increasing the proportion of early stage breast cancer patients suitable to receive PBI, even if the CVS is less favorable. Citation Format: Christine Anne Koch, Gemma Corey, Kathy Han, Grace Lee, Tom Purdie, Chris McIntosh, Patricia Lindsay, Fei-Fei Liu, Anthony Fyles, Wilf Levin, Jennifer Croke, Aisling Barry, Danielle Rodin, Nhu Tram Nguyen, Tatiana Conrad. Evaluation of partial breast irradiation suitability in early stage breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-24.

Motivation: Clinical evidence has shown that accelerated partial breast irradiation (APBI) for early stage breast cancer patients result in local recurrence control rates and cosmetic outcomes comparable to whole breast irradiation. Approaches to APBI include brachytherapy, intraoperative radiation therapy and external beam radiation therapy (EBRT). EBRT is the least invasive approach, most widely available, and does not require additional training. For EBRT APBI, based on NSABP B39/RTOG 0413 protocol, the clinical target volume (CTV) is generated by applying a 1.5 cm margin to the lumpectomy bed and the planning target volume (PTV) is generated by applying an additional 1 cm margin from the CTV to account for set up uncertainties.Real-time magnetic resonance imaging guided radiation therapy (MRgRT) allow for reduced treatment margins by decreasing treatment setup uncertainties. In this work, we share our experience in implementing a MRI guided accelerated partial breast irradiation (MRgAPBI) program into a new clinic with a linear accelerator capable of real-time MRI imaging. Methods: We have surveyed institutions in which rely on MRI guidance for APBI treatments through a comprehensive literature review and onsite visits. These visits included our radiation therapists, physicists, and radiation oncologists. There are two main components in implementing a new radiotherapy program: 1) patient simulation and immobilization techniques, and 2) treatment planning and delivery techniques. These techniques were studied and modified for our clinical workflow. Results: Literature review revealed a single institution report addressing their MRgAPBI experience. For immobilization, we adopted two techniques observed during two site visits. However, these techniques were later modified to allow for patient customization. For small breasted patients, a foam tube placed along the sternum is used and for large breasted patients, we employed custom made acrylic brackets placed superior to the shoulders which are then built into the patient's immobilization cradle for individualized set up. For patient comfort, the contralateral arm is placed down along the patient’s side, whereas the ipsilateral arm is moved up away from the radiation field. This also allows for lateral clearance for beam selection. For treatment planning, consensus on optimal margin for expansion from the lumpectomy bed is of utmost importance. A single institution MRgAPBI report described a 1 cm expansion from the lumpectomy bed to PTV while NSABP B39 indicated a 2.5 cm expansion. This reduction in margin was justified by the utilization of real-time MRgRT. We have come to consensus to use a 1.5 cm expansion around the lumpectomy cavity, which accounts for the CTV expansion per NSABP B39 and to forgo the PTV expansion given the minimal setup uncertainty with online MRgRT. Our initial experience showed significant changes in the lumpectomy cavity shape and volume when the gap between patient simulation and the start of treatment exceeded a week. We have thus reduced the time between simulation and treatment to 1 week to address this issue. Conclusion: Implementing a new MRgAPBI program requires a comprehensive evaluation of available resources and published reports, as well as, team visits to expert MRgAPBI centers. Both immobilization techniques and lumpectomy margin expansions for treatment planning should be well thought of prior to starting a similar program. In our experience, time between simulation and treatment of 1 week showed minimal changes in the shape and size of the planning volume. Additional verification will need to be conducted within a prospective setting and larger cohort. In order to setup a successful program, teamwork is essential between all groups including radiation therapists, dosimetrists, physicists, and radiation oncologists. Citation Format: Eenas A. Omari, Jennifer Gambla, Hahn P. Mai, Muaiad Kittaneh, Tarita O. Thomas, Raymond B. Wynn, Anil Sethi, William Small Jr, Tamer Refaat. Implementing a real-time magnetic resonance imaging guided accelerated partial breast irradiation program [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-21.

Purpose: To compare the locoregional control achieved with whole breast irradiation (WBI) and accelerated partial breast irradiation (APBI) in women with ductal carcinoma in situ (DCIS). Methods: We used an institutional, IRB-approved database to retrospectively identify women with primary DCIS lesions less than 3 cm from 1995 to 2014, who underwent negative-margin breast conserving surgery (BCS) followed by either WBI or APBI. Cox-proportional hazard analysis was performed to estimate risks of in-breast tumor recurrence (IBTR) and regional nodal recurrence (RNR), adjusting for age of patient at diagnosis. Results: Three-hundred and eighty women were identified. Seventy-nine percent received WBI and 21% underwent APBI. Among women receiving WBI, 15.4% received a sequential lumpectomy cavity boost. APBI was delivered via high-dose-rate (HDR) brachytherapy technique, utilizing either a multi-catheter interstitial or single-entry intracavitary approach. The median follow-up time was 6 years for women who received WBI, and 8.9 years for women who received APBI. The actuarial 10-year IBTR rate was 9.0% for WBI and 8.75% for APBI (p = 0.94). The actuarial 10-year isolated regional nodal recurrence (RNR) rate was 0% for WBI and 2.5% for APBI. Among women who received WBI, the 10-year IBTR rate was 10.0% without lumpectomy cavity boost and 6.36% with boost (p = 0.40). Increasing age correlated with a lower risk of recurrence, regardless of treatment modality (p = 0.005). Conclusions: No differences in locoregional control was detected for women with DCIS measuring Citation Format: Katarina T Nguyen, David Francis, Thevaa Chandering, Kelli Pointer, Bethany Anderson. Clinical outcomes achieved with brachytherapy vs whole breast irradiation for ductal carcinoma in situ [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-16-05.

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

Purpose: To assess the cosmetic impact of breast conserving surgery (BCS), whole breast irradiation (WBI) fractionation and tumour bed boost (TBB) use in a phase III trial for women with ductal carcinoma in situ (DCIS) of the breast. Materials and methods: Baseline and 3-year cosmesis were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System and digital images in a randomised trial of non-low risk DCIS treated with postoperative WBI +/− TBB. Baseline cosmesis was assessed for four geographic clusters of treating centres. Cosmetic failure was a global score of fair or poor. Cosmetic deterioration was a score change from excellent or good at baseline to fair or poor at three years. Odds ratios for cosmetic deterioration by WBI dose-fractionation and TBB use were calculated for both scoring systems. Results: 1608 women were enrolled from 11 countries between 2007 and 2014. 85–90% had excellent or good baseline cosmesis independent of geography or assessment method. TBB (16 Gy in 8 fractions) was associated with a >2-fold risk of cosmetic deterioration (p < 0.001). Hypofractionated WBI (42.5 Gy in 16 fractions) achieved statistically similar 3-year cosmesis compared to conventional WBI (50 Gy in 25 fractions) (p ≥ 0.18). The adverse impact of a TBB was not significantly associated with WBI fractionation (interaction p ≥ 0.30). Conclusions: Cosmetic failure from BCS was similar across international jurisdictions. A TBB of 16 Gy increased the rate of cosmetic deterioration. Hypofractionated WBI achieved similar 3-year cosmesis as conventional WBI in women treated with BCS for DCIS.

Background: Irradiation of the adjacent critical structures is inevitable in breast cancer radiotherapy (RT). Our purpose is to assess the dose distribution across the breast tissue and adjacent organs with our institutional asymmetric technique for left-sided breast cancer compared to the standard tangential wedged beam (TWB) and electron-boosted TWB techniques. Materials and Methods: The three RT planning were created for 30 consecutive patients with a focus on proper coverage of the planning target volume (PTV). The irritated doses into the heart, ipsilateral lung, and left anterior descending artery (LAD) were evaluated. Results: No significant difference was found in the mean values of relative PTV irradiated to 47.5 Gy, PTV dose and the volume of PTV, and critical organs between the treatments. The mean dose (Dmean) irradiated to the heart and LAD was lowest with the electron-boosted TWB. The Dmean to the heart was comparable between the TWB and asymmetric RT techniques, while the Dmean to LAD was significantly reduced with asymmetric technique versus TWB. The heart volume receiving ≥25 Gy and the Dmean to the left lung were significantly decreased with the asymmetric technique compared with TWB. The mean relative lung volume irradiated to ≥20 Gy was comparable between all techniques. The mean central lung distance was also significantly increased from 18.03 ± 4.5 cm with asymmetric RT to 37.47 ± 5.6 cm with TWB and to 27.67 ± 3.8 cm with electron-boosted TWB techniques. Conclusion: The asymmetric technique is useful for patients with breast cancer on the left side, having acceptable PTV coverage and considerably reduced cardiopulmonary doses.

Breast cancer is the most common noncutaneous malignancy in women. The prevalence increases with age such that nearly 7% of women in the United States over age 70 will be diagnosed with breast cancer. Radiation therapy (RT) is a standard component of the treatment course for women of all ages with breast cancer. RT is commonly encountered in the adjuvant setting for women with nonmetastatic disease, but also works for disease palliation in women with metastatic or recurrent disease. Different techniques for delivering RT for breast cancer include whole breast irradiation (WBI), accelerated partial-breast irradiation (APBI), and chest wall irradiation. Although these techniques often employ external beam radiation therapy (EBRT) delivered with photons, proton beam radiation therapy (PBRT) may also be used for each of these methods. Dosimetric breast cancer studies demonstrate clinical benefits of PBRT compared to photon EBRT. PBRT reduces the radiation dose delivered to the heart, particularly in women with left-sided breast cancer. This may subsequently reduce cardiac toxicity and associated cardiovascular disease. PBRT minimizes radiation dose to the lung and secondary tissues resulting in reduced pulmonary toxicity and secondary malignancies, respectively. PBRT offers superior target homogeneity and lymphatic coverage possibly leading to a lower risk of disease recurrence. A phase 3 prospective randomized clinical trial is currently being conducted to evaluate the efficacy of PBRT compared to EBRT with photons in patients with stage II–III breast cancer. Patients over age 70 with favorable stage I breast cancer may omit adjuvant RT. Elderly patients who are candidates for WBI, APBI and chest wall irradiation can receive PBRT and enjoy the same aforementioned benefits with potentially less toxicities. PBRT also plays a role in disease palliation and definitive therapy in patients who are not surgical candidates. In the elderly population, screening tests, such as the Timed Up and Go and G-8, can help determine which patients are suitable candidates for PBRT.

Background: Breast-conserving therapy including lumpectomy and adjuvant whole breast irradiation (WBI) has become the standard therapy for early-stage breast cancer (EBC). Without WBI, the recurrence rate is significantly increased. However, when selecting patients at a low a priori risk of local recurrence only a small breast-cancer-specific mortality benefit, but no overall survival improvement, was detected for WBI. As most recurrences occur close to the lumpectomy cavity, accelerated partial breast irradiation (APBI) delivered exclusively to a limited volume of tissue around the initial lumpectomy site, has gained increased attention and is now discussed as an alternative to WBI for selected EBC patients. Summary: Numerous techniques for APBI (interstitial brachytherapy, external beam-based APBI, intraoperative radiotherapy, MR-guided radiotherapy) allow treatment delivery in a shorter period of time, and radiation oncologists expect to further reduce side effects by using these new techniques, with improvements in cosmetics and quality of life. In this review, we aim to describe the existing evidence for the feasibility and effectiveness of different APBI techniques used in modern radiotherapy. Key Messages: APBI has provided outcomes similar to WBI combined with potentially reduced toxicity. While appropriate patient selection persists to be crucial for acceptable recurrence rates, the precise definition of patients suitable for APBI remains a matter of discussion. As long-term data are often still lacking, special attention should be paid to late side effects and long-term outcomes. Decision-making on appropriate treatment techniques should take into account not only local control rates, but also the impact on the patient’s quality of life.

Purpose Superficial dose is an important parameter in breast cancer radiation therapy. When treated with conventional linacs, bolus is commonly applied to improve target coverage near the surface while also managing the risk of severe skin reactions and negative cosmesis. With the introduction of modern linacs with 6X flattening filter free (FFF) photon beams, the effect on superficial dose and the need for bolus must be evaluated. Methods and Materials In vivo measurements of superficial dose were made with optically stimulated luminescence dosimeters on 11 breast cancer patients treated with the Halcyon 6X FFF linac (Varian Medical Systems, Palo Alto, CA). Additionally, measurements were made with the Halycon 6X FFF beam and a 6X beam with flattening filter (FF) delivered to an anthropomorphic phantom. A planning study was carried out in which 14 patients treated on the Halcyon were replanned with a conventional linac to determine the difference in superficial dose predicted by the treatment planning system. Measures were taken to increase the accuracy of the treatment planning system superficial dose. Results The use of the Halcyon 6X FFF beam led to higher superficial dose compared with 6X FF beams. The in vivo measurements show an average superficial dose of 83.8% ± 0.6%, which is an increase of approximately 10% compared with published measurements for a 6X FF linac. Comparison of superficial dose for 6X FF and 6X FFF beams in the phantom measurements show an increase from 70% ± 1.3% to 84% ± 1.3%, which is consistent with the in vivo measurements. The planning comparison shows an increase in V70%Rx from 62% ± 4.4% to 81% ± 2.2% for the superficial breast tissue for the Halcyon 6X FFF beam compared with a standard C-arm linac with FF. Conclusions The use of the Halcyon 6X FFF beam was associated with higher superficial dose which may obviate the use of bolus.

PURPOSE To compare radiation dose to organs at risk in patients with early-stage breast cancer treated with lumpectomy and intraoperative radiation therapy with CT-guided HDR brachytherapy (precision breast IORT; PB-IORT) and those treated with external beam whole breast irradiation (WB-DIBH) or partial breast irradiation (PB-DIBH) with deep inspiratory breath hold. METHODS We retrospectively identified 52 consecutive patients with left-sided breast cancers treated with either PB-IORT (n = 17, 76% outer breast) on a phase I clinical trial, adjuvant PB-DIBH (n = 18, 56% outer breast, 6% cavity boost), or WB-DIBH (n = 17, 76% outer breast, 53% with lumpectomy cavity boost). Conventional (2 Gy/fraction) or moderate hypofractionation (2.66 Gy/fraction) was prescribed for the external beam cohorts and 12.5 Gy in 1 fraction to 1 cm from the balloon surface was prescribed to the HDR brachytherapy cohort. CT-based planning was used for all patients. Organ at risk doses and excess risk ratios (ERR) for secondary lung cancers, contralateral breast cancers, and cardiac toxicity were compared between treatment techniques. RESULTS Compared to WB-DIBH and PB-DIBH, PB-IORT resulted in lower ipsilateral lung V5, V10, V20, mean, and max dose (P

Adjuvant radiation therapy is often delivered after breast cancer surgery, both in the post-lumpectomy and post-mastectomy settings. Standard fractionation whole breast irradiation (SF-WBI), which is typically delivered over 5-7 weeks, was previously considered the standard of care. More recent data has helped to establish hypofractionated whole breast irradiation (HF-WBI), which consists of a 3-4 week regimen, as a new standard of care. This article provides an overview of the major randomized trials that support the routine use of HF-WBI for the majority of patients undergoing breast-conserving surgery for early-stage breast cancer. Newer data on the use of a hypofractionated approach in the post-mastectomy setting, as well as ongoing randomized trials addressing this topic, are also discussed.

Summary Background Whole breast irradiation delivered once per day over 3–5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. Methods We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5–8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov , NCT00282035 . Findings Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3–9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9–4·0) in the APBI group and 2·8% (1·8–3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84–1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p Interpretation External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. Funding Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

Adjuvant irradiation is the standard treatment after breast conservative surgery. Normofractionated regimen with an overall treatment time of 5 to 6 weeks is often considered as a limiting factor for irradiation compliance. In order to answer this issue, moderate and more recently extreme hypofractionated protocols appeared. We report here oncological outcomes and toxicity of hypofractionated breast irradiation. After defining the frame of moderate and extreme hypofractionated breast irradiations based on overall treatment time, patient selection criteria were listed. According to their levels of proof, the results of moderate and extreme hypofractionated breast irradiation were analysed. Overall treatment time for moderate hypofractionated breast irradiation ranged from 3 to 4 weeks, while for extreme hypofractionated breast irradiation, it was less than 1 week. For moderate hypofractionated breast irradiation, whole breast irradiation was currently performed with or without lymph node irradiation. Moderate hypofractionated breast irradiation has proven to be as safe and as efficient as normofractionated breast irradiation with level IA evidence. For extreme hypofractionated breast irradiation, phase III randomized trials confirmed that accelerated partial breast irradiation was non-inferior in terms of local control compared to normofractionated whole breast irradiation (with external beam radiation therapy and multicatheter brachytherapy), with similar acute and late toxicity. While the use of intraoperative breast irradiation remains under debate, new very accelerated partial breast irradiation (overall treatment time not exceeding 2 days) protocols emerged with encouraging results. Accelerated partial breast irradiation is warranted for extreme hypofractionated breast irradiation and is indicated for low-risk breast cancers. Moderate and extreme hypofractionated breast irradiation regimens are validated and can be routinely proposed according to patient selection criteria.

Background Infiltration of the breast by leukemic cells is uncommon but may manifest as an oncological emergency requiring prompt management. Extramedullary relapse of T-cell acute lymphoblastic leukemia (T-ALL) within the breast is exceedingly rare and there is paucity of data in the literature regarding this entity. No consensus exists on management of isolated extramedullary breast relapses of T-ALL. Herein, we report a case of isolated extramedullary breast relapse of T-ALL treated with breathing adapted radiation therapy (BART) using the active breathing control (ABC) system. Case summary The patient was a 33-year-old female with diagnosis of T-ALL. She received intensive systemic chemotherapy that resulted in complete remission of her disease, and then underwent allogeneic hematopoietic stem cell transplantation. After a 15 mo period without symptoms and signs of progression, the patient presented with palpable masses in both breasts. She complained from severe pain and swelling of the breasts. Imaging workup showed bilateral breast lesions, and diagnosis of breast infiltration by leukemic cells was confirmed after immunohistopathological evaluation. The patient suffering from severe pain, discomfort, and swelling of both breasts due to leukemic infiltration was referred to the Radiation Oncology Department for symptomatic palliation. Whole breast irradiation was delivered to both breasts of the patient with BART using the ABC system. The patient had complete resolution of her symptoms after treatment with BART. Conclusion BART with the ABC system resulted in complete resolution of the patient's symptoms due to leukemic infiltration of both breasts with T-ALL. This contemporary treatment technique should be preferred for radiotherapeutic management of patients with leukemic infiltration of the breasts to achieve effective symptomatic palliation.

Purpose To evaluate the opportunities of single photon emission tomography/computerized tomography (SPECT-CT) for localization of axillary sentinel lymph nodes (ASLNs) and subsequent radiotherapy planning in women with early breast cancer. Material and methods Individual topography of ASLN was determined in 151 women with clinical T1-2N0M0 breast cancer. SPECT-CT visualization of ASLNs was initiated 120 min after intra-peritumoral injection of 99mTc-radiocolloids. Doses absorbed by virtual ASLNs after the whole breast irradiation with standard and extended tangential fields were calculated on a treatment planning station. Results SPECT-CT demonstrated a large variability of ASLN localization. They were detected in the central subgroup in 94 (61%) patients, in pectoral – in 77 (51%), and in interpectoral – in 4 (3%) patients. Sentinel lymph nodes “lying on the chest” were revealed in 35 (23%) cases. We found that with standard tangential fields coverage of ASLNs was obtained only in 20% of evaluated women. Extended tangential fields can effectively irradiate ASLNs localized in all axillary sub-regions with the exception of ASLNs “lying on the chest”. Conclusion SPECT-CT mapping of ASLNs in women with cT1-2N0M0 breast cancer reveals their variable localization. This information can be important for planning of radiation treatment in women that underwent breast conserving surgery without an axillary surgery.

Purpose To develop an automated workflow for whole breast irradiation treatment planning using hybrid intensity modulated radiation therapy (IMRT) approach and to demonstrate that this workflow can improve planning quality and efficiency when compared to manual planning. Methods The auto planning framework was built based on scripting with MIM and Pinnacle systems. MIM workflows were developed to automatically segment normal structures and targets, identify landmarks for beam placement, select beam energies, and set beam configurations. Pinnacle scripts were generated from the MIM workflow to create hybrid IMRT plans automatically. Each hybrid IMRT plan included two prescriptions: a three‐dimensional (3D) prescription consisted of two open tangent beams, and an IMRT prescription consisted of two step‐and‐shoot IMRT beams. The 3D prescription delivered a full prescription dose to the maximum dose point, and the IMRT prescription was optimized to deliver a uniform dose to the entire breast while sparing dose to the normal structures. For 30 patients, the auto plans were compared with clinically accepted manual plans using the paired sample t‐test. Results The auto planning process took approximately 8 min to complete. The mean dice coefficients between auto‐segmentation and manual contours were 0.98, 0.94 and 0.88 for the lungs, heart, and PTVeval_Breast, respectively. The MUs of the auto plans was on average 13% higher than that of the manual plans. Auto planning improved plan quality significantly: percentage volume receiving 95% of the prescription dose (V95%) of the PTVeval_Breast increased from 91.5% to 93.2% (P = 0.001), V105% of the PTVeval_Breast decreased from 7.2% to 1.2% (P = 0.013), V20Gy of the ipsilateral lung decreased from 13.1% to 10.4% (P = 0.001) and mean heart dose for left‐sided breast patients decreased from 1.2 Gy to 0.9 Gy (P

Background Whole breast irradiation reduces loco-regional recurrence and risk of death in patients submitted to breast-conserving treatment. Data show that radiation to the index quadrant alone may be enough in selected patients. Aim To report the experience with intra-operative radiotherapy (IORT) with Electron-beam Cone in Linear Accelerator (ELIOT) and the results in overall survival, local control and late toxicity of patients submitted to this treatment. Materials and Methods 147 patients treated with a median follow up of 6.9 years (0.1⿿11.5 years). The actuarial local control and overall survival probabilities were estimated using the Kaplan Meier method. All tests were two-sided and p ⿤ 0.05 was considered statistically significant. Results Overall survival of the cohort in 5 years, in the median follow up and in 10 years was of 98.3%, 95.1% and 95.1%, respectively, whereas local control in 5 years, in the median follow up and in 10 years was of 96%, 94.9% and 89.5%, respectively. Two risk groups were identified for local recurrence depending on the estrogen or progesterone receptors, axillary or margin status and lymphovascular invasion (LVI) (p = 0.016). Conclusions IORT is a safe and effective treatment. Rigorous selection is important to achieve excellent local control results.

Introduction of sentinel lymph node biopsy, initially in clinically node-negative and subsequently in patients presenting with involved axilla and downstaged by primary systemic therapy, allowed for significant decrease in morbidity compared to axillary lymph node dissection. Concurrently, regional nodal irradiation was demonstrated to improve outcomes in most node-positive patients. Additionally, over the last decades, introduction of more effective systemic therapies has resulted in improvements not only at distant sites, but also in locoregional control, creating space for de-escalation of locoregional treatments. We discuss the data on de-escalation in axillary surgery and irradiation, both in patients undergoing upfront surgery and primary systemic therapy, with special emphasis on the feasibility of omission of nodal irradiation in patients undergoing primary systemic therapy. In view of the accumulating evidence, omission of axillary irradiation may be considered in clinically node-positive patients converting after primary systemic therapy to pathologically negative nodes on sentinel lymph node biopsy (preferably also with in-breast pCR), presenting with lower initial nodal stage, older age and were treated with breast-conserving surgery followed by whole breast irradiation. Omission of regional nodal irradiation in patients with aggressive tumor phenotypes achieving a pCR is under investigation. In patients undergoing preoperative endocrine therapy the adoption of axillary management strategies utilized in case of upfront surgery seems more suitable than those used in post chemotherapy-based primary systemic therapy setting.

Background: Wholebreast irradiation (WBI) after breast conserving surgery for DCIS reduces therisk of local recurrence including invasive recurrence. The objective of BIG3-07/TROG 07.01 is to test radiation dose escalation to the tumor bed (tumorbed boost) and fractionation sensitivity of whole breast irradiation (WBI) inpatients with non-low risk DCIS treated with breast conserving therapy. Methods: BIG3-07/TROG 07.01 is an international, multicenter, randomized, controlled, phase 3 trial. Eligible women were ≥18 years ofage with completely resected non-low risk DCIS defined as age Results: BetweenJune 2007 and June 2014, 1608 patients were randomized to have no boost (805patients) or boost (803 patients) after WBI. Conventional WBI was given in 831 patients(no boost in 416 patients; boost in 415 patients). Hypofractionated WBI wasgiven in 777 patients (no boost in 389 patients; boost in 388 patients). Adjuvantendocrine therapy was planned in 106 patients (13%) in the no boost group and105 patients (13%) in the boost group. Median follow-up was 6.6 years. The 5-yearfree-from- local recurrence rates were 93% in the no boost group and 97% in theboost group (hazard ratio, 0.47; 95% confidence interval [CI], 0.31 to 0.72;P Conclusions: Inwomen with non-low risk DCIS treatedwith breast conserving surgery, the addition of tumor bed boost followingconventional or hypofractionated WBI reduced local recurrence rates. There wasno difference in local recurrence rates between conventional WBI andhypofractionated WBI. (Registered with ClinicalTrials.gov, NCT00470236.) Citation Format: Boon Hui Chua, Emma Link, Ian Kunkler, Ivo Olivotto, Antonia Helen Westenberg, Timothy Whelan, Guenther Gruber, Breast International Group (BIG)-aisbl, Trans Tasman Radiation Oncology Group, Scottish Cancer Trials Breast Group, Canadian Cancer Trials Group, European Organization for Research and Treatment of Cancer, International Breast Cancer Study Group, Cancer Trials Ireland. A randomized phase III study of radiation doses and fractionation schedules in non-low risk ductal carcinoma in situ (DCIS) of the breast (BIG 3-07/TROG 07.01) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS2-04.

Background In-vivo dosimetry (IVD) is a patient specific measure of quality control and safety during radiotherapy. With regard to current reporting thresholds for significant occurrences in radiotherapy defined by German regulatory authorities, the present study examines the clinical feasibility of superficial electron paramagnetic resonance (EPR) IVD of cumulative total doses applied to breast cancer patients treated with helical intensity-modulated radiotherapy (tomotherapy). Methods In total, 10 female patients with left- or right-sided breast cancer were enrolled in this prospective IVD study. Each patient received a hypofractionated whole breast irradiation. A total median dose of 42.4 Gy in 16 fractions (5 fractions per week) was prescribed to the planning target volume. The treatments were completely delivered using helical tomotherapy and daily image guidance via megavoltage CT (MVCT). For each patient, three EPR dosimeters were prepared and placed at distinct locations on the patient’s skin during the delivery of all fractions. Two dosimeters were placed next to the ipsilateral and contralateral mammilla and one dosimeter was placed ventrally to the thyroid (out-of-primary-beam). The total doses delivered to the dosimeters were readout after all fractions had been administered. The measured total dose values were compared to the planned dose values derived from the treatment planning system (TPS). Daily positional variations (displacement vectors) of the ipsilateral mammilla and of the respective dosimeter were analyzed with respect to the planned positions using the daily registered MVCT image. Results Averaged over all patients, the mean absolute dose differences between measured and planned total dose values (± standard deviation (SD)) were: 0.49 ± 0.85 Gy for the ipsilateral dosimeter, 0.17 ± 0.49 Gy for the contralateral dosimeter and -0.12 ± 0.30 Gy for the thyroid dosimeter. The mean lengths of the ipsilateral displacement vectors (± SD) averaged over all patients and fractions were: 10 ± 7 mm for the dosimeter and 8 ± 4 mm for the mammilla. Conclusion Superficial EPR IVD is suitable as additional safeguard for dose delivery during helical tomotherapy of breast cancer. Despite positional uncertainties in clinical routine, the observed dose deviations at the ipsilateral breast were on average small compared to national reporting thresholds for total dose deviations (i.e. 10%/4 Gy). EPR IVD may allow for the detection of critical dose errors during whole breast irradiations.

BACKGROUND: Angiosarcoma may rarely complicate radiotherapy of breast cancer. This so-called radiation-induced angiosarcoma (RIAS) occurs in less than 0.3% of patients that underwent breast conservation surgeries, usually years after completion of radiotherapy. CASE PRESENTATION: we introduce two cases of invasive ductal carcinoma who underwent lumpectomy and accelerated partial breast irradiation (APBI) as an alternative protocol to whole breast irradiation (WBI). They received adjuvant partial breast radiotherapy on tumor cavity for a total dose of 38.5 Gy in 10 fractions in 5 days using 3D-external-beam RT. In both cases, RIAS occurred eight years after radiotherapy, in the sub-cicatricial area in one patient and outside the irradiated area in the other one. They both underwent radical surgery and chemotherapy was performed in one patient. DISCUSSION: The underlying mechanism for development of RIAS is not well known, but its incidence seems to be increasing. RIAS after partial breast irradiation is very rare and has been reported in two cases so far. As it may be suggested in case 2, it is still a matter of debate if the risk of radiation-induced sarcoma is radiation-dose dependent. Although mastectomy is considered as a standard treatment, choice of treatment should be made according to the patient’s specifications. CONCLUSION: There are very few studies in the literature that report RIAS after APBI. Present study is the only one reporting two cases after the external 3D technique APBI. Prognosis of RIAS remains poor. Only a careful evaluation in a multidisciplinary context can offer to the patients the best result in terms of local control and survival

Purpose For whole-breast irradiation after breast-conserving surgery, computed tomography simulation (CTS) and irradiation are generally performed during free breathing. In treatment planning, there are three techniques: field-in-field (FIF), physical wedge (PW), and enhanced dynamic wedge (EDW). The aim of this study was to investigate the impact of respiratory motion on doses for these three irradiation techniques. Methods All doses were measured using an ionization chamber in a cylindrical phantom on a respiratory motion platform. Doses for each technique were measured with and without phantom motion. The dose without phantom motion was defined as the reference. The reference was compared to the dose with the phantom motion. The positions of the isocenter with respect to the ranges of phantom motion were set as exhale and intermediate. The phantom motion amplitude was set to 5 mm or 10 mm. The respiratory phase to initiate irradiation was varied as inhale, intermediate-inhale, exhale and intermediate-exhale. Results When the motion amplitude was 10 mm, the dose differences for the FIF, PW, and EDW techniques were 4.2%, 0.5%, and 0.8%, respectively, at the maximum. However, the dose difference for the FIF technique was -0.5% when the isocenter position was set to the intermediate phase of phantom motion. Conclusion We found that the dose difference per fraction was reduced when the respiratory phase during CTS image acquisition was set to the intermediate phase. Meanwhile, the dose differences per fraction for the PW and EDW techniques were less affected by the respiratory motion.