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Background: The purpose of this real-world study was to investigate the risk factors for developing recurrence among patients with pathological T1-3N0 breast cancer (BC) treated with breast-conserving surgery (BCS) followed by whole breast irradiation alone (WBI) and identify those clinically high-risk BCs who could benefit from regional nodal irradiation (RNI). Materials and methods: Female BC patients treated at Shanghai Ruijin hospital from 2009 to 2016 were retrospectively reviewed. The disease-free survival (DFS), breast cancer specific survival (BCSS) and overall survival (OS) were estimated by the Kaplan-Meier method, and survival differences were compared with the log-rank test. Univariate and multivariate analysis was performed using Cox proportional hazards regression analysis. An external validation was conducted by using SEER database. Results: A total of 622 BC patients treated with BCS+WBI alone were included. With a median follow-up of 82 months, the 7-year OS, BCSS and DFS for the entire cohort was 97%, 99% and 91%, respectively. Multivariable Cox analysis indicated that tumor size (p=0.006), tumor location (p=0.033), lymphovascular invasion (LVI) status (p=0.0028) and Ki-67 index (p=0.051) were independent risk factors for DFS. A scoring system was developed using these four factors and the 7-year DFS and OS were 97% and 96% for patients with 0-1 risk factors, 95% and 82% for patients with ≥2 risk factors (p<0.0001 for DFS, and p=0.0063 for OS). Based on tumor size and tumor location, an external validation by demonstrated that the 7-year OS was 90% and 88% for patients with 0-1 risk factor, which was significantly better than those defined as high-risk BC patients (82%, p<0.0001). Conclusion: By using our institute database, we establish a risk stratification system for identifying sub-group of pN0 BC patients, who are at high risk for developing recurrence. The results of our study support tailored RT decisionmaking according to individual risks, which needed to be confirmed in further studies. [ABSTRACT FROM AUTHOR]

Simple Summary: This multicenter study (n = 1133, inclusion criteria: 3.5 cm maximum tumor size and preoperative indication for a boost) provides detailed data on acute and long-term toxicities in breast cancer patients undergoing breast-conserving surgery combined with an anticipated intraoperative boost with low-energy X-rays followed by whole breast irradiation. Toxicity assessments, based on LENT SOMA criteria, were performed annually up to 10 years of follow-up. IORT boost was completed in 90% and EBRT in 97% of cases. No grade 3 or 4 acute toxicities were observed, with mild acute side effects reported in a small proportion of patients. Chronic toxicities were seen in 16.2% of patients with teleangiectasia, 14.3% with grade ≥ 2 fibrosis, 3.4% with grade ≥ 2 pain, and 1.1% with hyperpigmentation. The results show that the therapy is safe and feasible in terms of toxicity and confirms intraoperative boost as a standard method of boost application in a large prospective cohort. In the context of breast cancer treatment optimization, this study prospectively examines the feasibility and outcomes of utilizing intraoperative radiotherapy (IORT) as a boost in combination with standard external beam radiotherapy (EBRT) for high-risk patients. Different guidelines recommend such a tumor bed boost in addition to whole breast irradiation with EBRT for patients with risk factors for local breast cancer recurrence. The TARGIT BQR (NCT01440010) is a prospective, multicenter registry study aimed at ensuring the quality of clinical outcomes. It provides, for the first time, data from a large cohort with a detailed assessment of acute and long-term toxicity following an IORT boost using low-energy X-rays. Inclusion criteria encompassed tumors up to 3.5 cm in size and preoperative indications for a boost. The IORT boost, administered immediately after tumor resection, delivered a single dose of 20 Gy. EBRT and systemic therapy adhered to local tumor board recommendations. Follow-up for toxicity assessment (LENT SOMA criteria: fibrosis, teleangiectasia, retraction, pain, breast edema, lymphedema, hyperpigmentation, ulceration) took place before surgery, 6 weeks to 90 days after EBRT, 6 months after IORT, and then annually using standardized case report forms (CRFs). Between 2011 and 2020, 1133 patients from 10 centers were preoperatively enrolled. The planned IORT boost was conducted in 90%, and EBRT in 97% of cases. Median follow-up was 32 months (range 1–120, 20.4% dropped out), with a median age of 61 years (range 30–90). No acute grade 3 or 4 toxicities were observed. Acute side effects included erythema grade 1 or 2 in 4.4%, palpable seroma in 9.1%, punctured seroma in 0.3%, and wound healing disorders in 2.1%. Overall, chronic teleangiectasia of any grade occurred in 16.2%, fibrosis grade ≥ 2 in 14.3%, pain grade ≥ 2 in 3.4%, and hyperpigmentation in 1.1%. In conclusion, a tumor bed boost through IORT using low-energy X-rays is a swift and feasible method that demonstrates low rates in terms of acute or long-term toxicity profiles in combination with whole breast irradiation. [ABSTRACT FROM AUTHOR]

BackgroundIntraoperative radiation therapy (IORT) and whole breast irradiation (WBI) are both effective adjuvant radiotherapy methods for ductal carcinoma in situ (DCIS) or early-stage breast cancer (BC) patients undergoing breast-conserving surgery (BCS). We aim to evaluate the long-term oncological efficacy and refine patient selection criteria based on our findings.MethodsFemale patients who underwent either IORT or WBI from January 2016 to December 2019, with a minimum follow-up of 12 months were collected. IORT was administered as a single fraction of 20 Gray (Gy) to the lumpectomy cavity using the Axxent electronic brachytherapy system, while WBI consisted of a standard fractionation of 50 Gy in 25 fractions, along with a reduced boost of 10 Gy. The clinicopathologic characteristics and oncological outcomes were retrospectively analyzed.ResultsA total of 247 patients were enrolled, comprising 164 with BC and 83 with DCIS. Among them, 112 underwent IORT, and 135 received WBI after BCS. The median age was 62.2 years, with median tumor sizes of 1.5 cm for BC and 1.2 cm for DCIS. At a median follow-up of 64.6 months, IORT demonstrated 11 locoregional recurrences (LRR), 1 metastasis, and 1 death, compared to 4 LRR, 5 metastases, and 2 deaths in the WBI group. WBI yielded significantly higher locoregional control (97.0% vs. 90.2%, p = 0.033), although metastasis-free (96.3% vs. 99.1%, p = 0.166) and overall survival rates (98.4% vs. 99%, p = 0.688) did not differ. The LRR rate was significantly higher in the IORT group among the DCIS or BC patients (p = 0.043). The hazard ratio for locoregional recurrence significantly increased in estrogen-receptor-negative (ER-) patients in both univariate analysis (HR = 4.98, 95% CI = 1.76-14.09, p = 0.002) and multivariate analysis (HR = 40.88, 95% CI = 1.29-1297.84, p = 0.035). Additionally, IORT was associated with increased LRR in the multivariate analysis (HR = 4.71, 95% CI = 1.16-19.06, p = 0.030).ConclusionAt a long-term follow-up, the LRR rate was higher in the BCS followed by IORT, without significant differences in metastasis-free or overall survival rates. Our data confirmed the importance of exclusion ER- patients for IORT.

The role of postmastectomy radiotherapy and regional nodal irradiation after radical mastectomy is defined in high-risk patients with locally advanced tumors, positive margins, and unfavorable biology. The benefit of postmastectomy radiotherapy in intermediate-risk patients (T3N0 tumors) remains a matter of controversy. It has been demonstrated that radiotherapy after breast-conserving surgery lowers the locoregional recurrence rate compared with surgery alone and improves the overall survival rate. In patients with four or more positive lymph nodes or extracapsular extension, regional lymph node irradiation is indicated regardless of the surgery type (breast-conserving surgery or mastectomy). Despite the consensus that patients with more than three positive lymph nodes should be treated with radiotherapy, there is controversy regarding the recommendations for patients with one to three involved lymph nodes. In patients with N0 disease with negative findings on axillary surgery, there is a trend to administer regional lymph node irradiation in patients with a high risk of recurrence. In patients treated with neoadjuvant systemic therapy and mastectomy, adjuvant radiotherapy should be administered in cases of clinical stage III and/or ≥ypN1. In patients treated with neoadjuvant systemic therapy and breast-conserving surgery, postoperative radiotherapy is indicated irrespective of pathological response.

The role of postmastectomy radiotherapy and regional nodal irradiation after radical mastectomy is defined in high-risk patients with locally advanced tumors, positive margins, and unfavorable biology. The benefit of postmastectomy radiotherapy in intermediate-risk patients (T3N0 tumors) remains a matter of controversy. It has been demonstrated that radiotherapy after breast-conserving surgery lowers the locoregional recurrence rate compared with surgery alone and improves the overall survival rate. In patients with four or more positive lymph nodes or extracapsular extension, regional lymph node irradiation is indicated regardless of the surgery type (breast-conserving surgery or mastectomy). Despite the consensus that patients with more than three positive lymph nodes should be treated with radiotherapy, there is controversy regarding the recommendations for patients with one to three involved lymph nodes. In patients with N0 disease with negative findings on axillary surgery, there is a trend to administer regional lymph node irradiation in patients with a high risk of recurrence. In patients treated with neoadjuvant systemic therapy and mastectomy, adjuvant radiotherapy should be administered in cases of clinical stage III and/or ≥ypN1. In patients treated with neoadjuvant systemic therapy and breast-conserving surgery, postoperative radiotherapy is indicated irrespective of pathological response. [ABSTRACT FROM AUTHOR]

Hui-Ling Yeh,1 Jia-Fu Lin2 1Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan; 2Division of Radiation Physics, Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, TaiwanCorrespondence: Jia-Fu Lin, Division of Radiation Physics, Department of Radiation Oncology, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Blvd., Xitun District, Taichung, Taiwan, Tel +886-423592525 &num;5601, Fax +886-423741316, Email yyj@vghtc.gov.twAim: To investigate the impact of DIBH for heart sparing effect on left sided breast postoperative whole breast irradiation by comparing the dosimetric characteristics of 3D-CRT hybrid VMAT and pure VMAT treatment planning under DIBH condition.Materials and Methods: The primary CT data sets from previously treated left sided early breast cancer were used for pure volumetric arc therapy (VMAT) technique re-planning for the dosimetric characteristics comparison. A treatment plan of 3D-CRT hybrid VMAT technique was re-planned on the free breath (FB) condition for the investigation of the dosimetric characteristics comparison on DIBH condition. The prescribed dose for all the treatment plans was 42.5Gy in 16 fractions. All plans were optimized to cover 100% of the PTV by 95% of prescribed dose. The dosimetric differences among the 3 treatment plans for the 20 patients were analyzed using Wilcoxon signed-rank test, with p value< 0.05 considered statistically significant.Results: 3D-CRT hybrid VMAT using DIBH technique yielded the best results on the conformity index (CI) and homogeneity index (HI). By comparing this 3D-CRT hybrid VMAT technique using FB and DIBH technique, the mean heart dose (MHD) was reduced from 5.38Gy to 1.65Gy, respectively (p =0.001) and the left anterior descending coronary artery (LAD)0.03cc dose was reduced from 27.87Gy to 9.41Gy, respectively (p =0.001). 3D-CRT hybrid VMAT using DIBH technique significantly reduced the V5, V20 and D mean of the ipsilateral lung and D mean of the contralateral lung. The D5 of right breast was significantly reduced by 3D-CRT hybrid VMAT compared with VMAT using DIBH technique.Conclusion: The incorporation of DIBH into 3D-CRT hybrid VMAT technique provides the best benefits for the heart and the OAR with respect to the radiation dose-sparing effect without compromising the target conformity and homogeneity in the treatment planning.Keywords: left sided breast cancer, postoperative radiotherapy, whole breast irradiation, DIBH, hybrid technique, heart dose-sparing

Purpose of Review: To review the current approaches to fractionation from phase III prospective randomized trials for postlumpectomy whole breast radiation therapy (WBRT) for early-stage breast cancer. Recent Findings: Moderate hypofractionation (M-WBRT) given Monday through Friday over 3–4 weeks is now standard practice for almost all patients needing postlumpectomy WBRT. The use of M-WBRT is being expanded to include regional node irradiation (RNI) and may be further shortened by a tumor bed boost that is concurrent rather than sequential to avoid extra days of treatment. And for selected patients, there is now an option for ultra-hypofractionation (U-WBRT) that further shortens WBRT to as few as 5 treatments in 1 week. Summary: When WBRT is indicated after lumpectomy for early-stage breast cancer, moderate hypofractionation over 3 weeks is the preferred radiation schedule for most patients. Select patients are eligible for a 1-week schedule using ultra-hypofractionation. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the dosimetric advantages of the voluntary deep inspiration breath-hold technique assisted by optical surface monitoring system for whole breast irradiation in left breast cancer after breast-conserving surgery and verify the reproducibility and acceptability of this technique. Methods: Twenty patients with left breast cancer receiving whole breast irradiation after breast-conserving surgery were enrolled in this prospective phase II study. Computed tomography simulation was performed during both free breathing and voluntary deep inspiration breath-hold for all patients. Whole breast irradiation plans were designed, and the volumes and doses of the heart, left anterior descending coronary artery, and lung were compared between free breathing and voluntary deep inspiration breath-hold. Cone beam computed tomography was performed for the first 3 treatments, then weekly during voluntary deep inspiration breath-hold treatment to evaluate the accuracy of the optical surface monitoring system technique. The acceptance of this technique was evaluated with in-house questionnaires completed by patients and radiotherapists. Results: The median age was 45 (27-63) years. All patients received hypofractionated whole breast irradiation using intensity-modulated radiation therapy up to a total dose of 43.5 Gy/2.9 Gy/15f. Seventeen of the 20 patients received concomitant tumor bed boost to a total dose of 49.5 Gy/3.3 Gy/15f. Voluntary deep inspiration breath-hold showed a significant decrease in the heart mean dose (262 ± 163 cGy vs 515 ± 216 cGy, P <.001) and left anterior descending coronary artery (1191 ± 827 cGy vs 1794 ± 833 cGy, P <.001). The median delivery time of radiotherapy was 4 (1.5-11) min. The median deep breathing cycles were 4 (2-9) times. The average score for acceptance of voluntary deep inspiration breath-hold by patients and radiotherapists was 8.7 ± 0.9 (out of 12) and 10.6 ± 3.2 (out of 15), respectively, indicating good acceptance by both. Conclusions: The voluntary deep inspiration breath-hold technique for whole breast irradiation after breast-conserving surgery in patients with left breast cancer significantly reduces the cardiopulmonary dose. Optical surface monitoring system–assisted voluntary deep inspiration breath-hold is reproducible and feasible and showed good acceptance by both patients and radiotherapists. [ABSTRACT FROM AUTHOR]

Simple Summary: Ultra-high dose-rate (UHDR) irradiation can lead to a FLASH-effect which reduces the biological effect on healthy tissue without affecting the dose to the tumor. UHDRs can currently be achieved using 250 MeV (transmission) proton beams. Up until now, suggested treatment sites potentially benefiting from a FLASH effect include, e.g., small lung, skin, and brain tumors. We suggest the use of FLASH for breast tumors because almost the entire target consists of healthy tissue and hypofractionated dose schedules are common. In this study, we demonstrate that whole breast irradiation (WBI) can be performed using a single transmission proton beam. We evaluated the necessary proton beam parameters in order to achieve the maximum FLASH-effect according to our current knowledge. Although currently not clinically applicable, we hypothesize that a potential FLASH-effect can even allow for further hypofractionation of WBI. Healthy tissue-sparing effects of FLASH (≥40 Gy/s, ≥4–8 Gy/fraction) radiotherapy (RT) make it potentially useful for whole breast irradiation (WBI), since there is often a lot of normal tissue within the planning target volume (PTV). We investigated WBI plan quality and determined FLASH-dose for various machine settings using ultra-high dose rate (UHDR) proton transmission beams (TBs). While five-fraction WBI is commonplace, a potential FLASH-effect might facilitate shorter treatments, so hypothetical 2- and 1-fraction schedules were also analyzed. Using one tangential 250 MeV TB delivering 5 × 5.7 Gy, 2 × 9.74 Gy or 1 × 14.32 Gy, we evaluated: (1) spots with equal monitor units (MUs) in a uniform square grid with variable spacing; (2) spot MUs optimized with a minimum MU-threshold; and (3) splitting the optimized TB into two sub-beams: one delivering spots above an MU-threshold, i.e., at UHDRs; the other delivering the remaining spots necessary to improve plan quality. Scenarios 1–3 were planned for a test case, and scenario 3 was also planned for three other patients. Dose rates were calculated using the pencil beam scanning dose rate and the sliding-window dose rate. Various machine parameters were considered: minimum spot irradiation time (minST): 2 ms/1 ms/0.5 ms; maximum nozzle current (maxN): 200 nA/400 nA/800 nA; two gantry-current (GC) techniques: energy-layer and spot-based. For the test case (PTV = 819 cc) we found: (1) a 7 mm grid achieved the best balance between plan quality and FLASH-dose for equal-MU spots; (2) near the target boundary, lower-MU spots are necessary for homogeneity but decrease FLASH-dose; (3) the non-split beam achieved >95% FLASH for favorable (not clinically available) machine parameters (SB GC, low minST, high maxN), but <5% for clinically available settings (EB GC, minST = 2 ms, maxN = 200 nA); and (4) splitting gave better plan quality and higher FLASH-dose (~50%) for available settings. The clinical cases achieved ~50% (PTV = 1047 cc) or >95% (PTV = 477/677 cc) FLASH after splitting. A single UHDR-TB for WBI can achieve acceptable plan quality. Current machine parameters limit FLASH-dose, which can be partially overcome using beam-splitting. WBI FLASH-RT is technically feasible. [ABSTRACT FROM AUTHOR]

Abstract Background To implement a tangential treatment technique for whole breast irradiation using the Varian Halcyon and to compare it with Elekta Synergy Agility plans. Methods For 20 patients two comparable treatment plans with respect to dose coverage and normal tissue sparing were generated. Tangential field-in-field treatment plans (Pinnacle/Synergy) were replanned using the sliding window technique (Eclipse/Halcyon). Plan specific QA was performed using the portal Dosimetry and the ArcCHECK phantom. Imaging and treatment dose were evaluated for treatment delivery on both systems using a modified CIRS Phantom. Results The mean number of monitor units for a fraction dose of 2.67 Gy was 515 MUs and 260 MUs for Halcyon and Synergy Agility plans, respectively. The homogeneity index and dose coverage were similar for both treatment units. The plan specific QA showed good agreement between measured and calculated plans. All Halcyon plans passed portal dosimetry QA (3%/2 mm) with 100% points passing and ArcCheck QA (3%/2 mm) with 99.5%. Measurement of the cumulated treatment and imaging dose with the CIRS phantom resulted in lower dose to the contralateral breast for the Halcyon plans. Conclusions For the Varian Halcyon a plan quality similar to the Elekta Synergy device was achieved. For the Halcyon plans the dose contribution from the treatment fields to the contralateral breast was even lower due to less interleaf transmission of the Halcyon MLC and a lower contribution of scattered dose from the collimator system.

Purpose: We sought to explore the role of nomogram-combined biomarkers, mammographic microcalcification and inflammatory hematologic markers in guiding local therapy decisions in ductal carcinoma in situ (DCIS) subgroups with different ipsilateral breast tumour recurrence (IBTR) risk. Methods: Between January 2009 and December 2018, consecutive patients with DCIS and breast conserving surgery (BCS) were enrolled and randomly assigned to a training cohort (n = 181) and internally validation cohort (n = 78). Multivariate analyses were performed to identify predictors of IBTR. Model performance was evaluated by the concordance index (C-index) and calibration plot. The time-to-event curves were calculated by the Kaplan–Meier methods and compared by the log-rank test. Results: In total, 259 patients were enrolled and 182 of them received whole breast irradiation (WBI). After a median follow-up of 51.02 months, 23 IBTR events occurred in the whole cohort. By multivariate analyses of training cohort, presence of microinvasion, Ki67 index >14%, mammographic-clustered fine linear microcalcifications and neutrophil/lymphocyte ratio before BCS (preop-NLR), >1.1 remained independent risk factors of IBTR to develop a nomogram. The C-indexes of the nomogram were 0.87 and 0.86 in the training and internal validation set, respectively. Calibration plots illustrated good agreement between the predictions and actual observations for 5-year IBTR. Cut-off values of nomogram point were identified as 53 and 115 points, which divided all patients into low-, intermediate- and high-risk groups. Significant differences in IBTR existed between low-, intermediate- and high-risk subgroups (p < 0.01). For the whole cohort and ER-positive tumours, the benefit of WBI was found only in the intermediate-risk subgroup, but not in those with low or high risk. Fourteen out of 23 IBTRs occurred outside the original quadrant and all occurred in the high-risk group. Conclusions: The novel nomogram demonstrated potential to separate the risk of IBTR and locations of IBTR. For the whole cohort and ER-positive tumours, the benefit of WBI was restricted to an intermediate-risk subgroup. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association between irradiated breast volume and grade 2-3 breast induration three years after radiotherapy in the phase III Danish Breast Cancer Group HYPO trial randomizing patients ≥ 41 years to whole breast irradiation (WBI) with 40 Gy/15fr versus 50 Gy/25fr., Methods: Treatment plans were available for all Danish patients. Associations between frequency of induration and irradiated volume, age, smoking status, and boost were assessed by logistic regression. A sequential boost was given to patients < 50 years or in case of a narrow (<2 mm) resection margin., Results: RT plans from 1,333 patients were analyzed with 178 (13 %) having grade 2-3 induration. 1135 patients had only WBI. For this group, induration was correlated with irradiated breast volume for patients ≥ 65 years (n = 343, 10 %/22 % for small/large irradiated volumes, p = 0.005) but not for patients aged 50-64 years (n = 792, 11 % for both small and large volumes, p = 0.82). Smoking doubled the frequency irrespective of irradiated volume and age. All patients < 50 years (n = 156) had a boost. A volume effect was found for this group (5 %/21 % induration for small/large volume, p = 0.002). 42 patients ≥ 50 years had a boost and 14 (33 %) had grade 2-3 induration, however, with a p-value > 0.05 due to the few numbers of patients., Conclusion: A relationship between irradiated breast volume and 3-year frequency of breast induration was found for patients ≥ 65 years, whilst not for patients aged 50-64 years. Smoking doubled the risk of induration irrespective of volume and age. A dose-induration relationship was seen for boost patients < 50 years., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The purpose of this real-world study was to investigate the risk factors for developing recurrence among patients with pathological T1-3N0 breast cancer (BC) treated with breast-conserving surgery (BCS) followed by whole breast irradiation alone (WBI) and identify those clinically high-risk BCs who could benefit from regional nodal irradiation (RNI)., Materials and Methods: Female BC patients treated at Shanghai Ruijin hospital from 2009 to 2016 were retrospectively reviewed. The disease-free survival (DFS), breast cancer specific survival (BCSS) and overall survival (OS) were estimated by the Kaplan-Meier method, and survival differences were compared with the log-rank test. Univariate and multivariate analysis was performed using Cox proportional hazards regression analysis. An external validation was conducted by using SEER database., Results: A total of 622 BC patients treated with BCS+WBI alone were included. With a median follow-up of 82 months, the 7-year OS, BCSS and DFS for the entire cohort was 97%, 99% and 91%, respectively. Multivariable Cox analysis indicated that tumor size ( p =0.006), tumor location ( p =0.033), lymphovascular invasion (LVI) status ( p =0.0028) and Ki-67 index ( p =0.051) were independent risk factors for DFS. A scoring system was developed using these four factors and the 7-year DFS and OS were 97% and 96% for patients with 0-1 risk factors, 95% and 82% for patients with ≥2 risk factors ( p <0.0001 for DFS, and p =0.0063 for OS). Based on tumor size and tumor location, an external validation by demonstrated that the 7-year OS was 90% and 88% for patients with 0-1 risk factor, which was significantly better than those defined as high-risk BC patients (82%, p <0.0001)., Conclusion: By using our institute database, we establish a risk stratification system for identifying sub-group of pN0 BC patients, who are at high risk for developing recurrence. The results of our study support tailored RT decision-making according to individual risks, which needed to be confirmed in further studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qi, Cao, Ou, Li, Xu, Cai, Xu, Cai and Chen.)

Abstract Purpose To use cone-beam computed tomography (CBCT) imaging to determine the impacts of patient characteristics on the magnitude of geometric setup errors and obtain patient-specific planning target volume (PTV) margins from the correlated patient characteristics in whole breast irradiation (WBI). Methods Between January 2019 and December 2019, a total of 97 patients who underwent breast-conserving surgery, followed by intensity-modulated radiation therapy in WBI, were scanned with pre-treatment CBCT for the first three treatment fractions and weekly for the subsequent fractions. Setup errors in the left–right (LR), superior–inferior (SI) and anterior–posterior (AP) directions were recorded and analyzed with patient characteristics—including age, tumor location, body mass index (BMI), chest circumference (CC) and breast volume (BV)—to examine the predictors for setup errors and obtain specific PTV margins. Results A total of 679 CBCT images from 97 patients were acquired for analysis. The mean setup errors for the whole group were 2.32 ± 1.21 mm, 3.71 ± 2.21 mm and 2.75 ± 1.56 mm in the LR, SI and AP directions, respectively. Patients’ BMI, CC and BV were moderately associated with setup errors, especially in the SI directions (R = 0.40, 0.43 and 0.22, respectively). Setup errors in the SI directions for patients with BMI > 23.8 kg/m2, CC > 89 cm and BV > 657 cm3 were 4.56 ± 2.59 mm, 4.77 ± 2.42 mm and 4.30 ± 2.43 mm, respectively, which were significantly greater than those of patients with BMI ≤ 23.8 kg/m2, CC ≤ 89 cm and BV ≤ 657 cm3 (P 23.8 kg/m2, CC > 89 cm and BV > 657 cm3 were 4.25/7.95/4.93 mm, 4.37/7.66/5.24 mm and 4.22/7.54/5.29 mm in the LR/SI/AP directions, respectively, compared with 3.64/4.64/5.09 mm, 3.31/4.50/4.82 mm and 3.29/5.74/4.73 mm for BMI ≤ 23.8 kg/m2, CC ≤ 89 cm and BV ≤ 657 cm3, respectively. Conclusions The magnitude of geometric setup errors was moderately correlated with BMI, CC and BV. It was recommended to set patient-specific PTV margins according to patient characteristics in the absence of daily image-guided treatment setup.

La radiothérapie hypofractionnée modérée est devenue une pratique de routine pour une population sélectionnée de patientes traitées pour un cancer du sein de stade précoce. En avril 2020 est publiée l'étude Fast Forward qui introduit un autre schéma de radiothérapie hypofractionnée extrême en cinq séances sur une semaine. L'objectif de ce travail était d'évaluer la population de premières patientes chez qui ce schéma a été utilisé dans notre département, ainsi que les résultats en termes de toxicité précoce. Nous avons rétrospectivement analysé toutes les patientes traitées dans notre département selon le protocole Fast Forward après la sortie de la publication originale et après établissement d'un consensus institutionnel vis-à-vis de la sélection des patientes atteintes d'un cancer du sein sans indication à une irradiation ganglionnaire. Toutes les patientes ont reçu une irradiation du sein seul à la dose totale de 26 Gy en cinq fractions conformément au protocole. Toutes les patientes ont été traitées par des techniques modernes conformationnelles avec une couverture du volume cible prévisionnel entre 95 et 100 %. La toxicité aiguë du traitement a été évaluée à l'aide de l'échelle du National Cancer Institute (NCI) des Common Toxicity Criteria (CTC) v4.0 et l'état général a été évalué selon la classification de l'Organisation mondiale de la santé. Entre août 2020 et mai 2021, 30 patientes ont été incluses, traitées dans le sein seul sans complément dans le lit tumoral ni irradiation des aires ganglionnaires. L'âge médian des patientes était 80 ans (entre 60 et 85 ans) avec un état général moyen OMS 2 dans 27 cas (90 %). Une seule patiente était atteinte d'une maladie métastatique (3 %), et 29 (97 %) patientes étaient atteintes d'une maladie de stade précoce. Trois patientes (10 %) ont été traitées en décubitus dorsal selon la technique « champ dans le champ » et 27 patientes (90 %) en décubitus latéral isocentrique, qui a permis d'éviter les organes à risque comme le cœur (dose moyenne de moins d'1 Gy) et les poumons. La toxicité précoce observée était une radiodermite de grade I chez huit patientes (27 %). Aucun cas de douleurs ou lymphœdème radio-induits n'a été observé. Les résultats de cette série de patientes traitées par une irradiation hypofractionnée selon le protocole Fast Forward sur le sein seul avec des techniques adaptées montrent que le protocole est faisable, avec peu de toxicité précoce mais un recul plus important est nécessaire pour évaluer la toxicité à long terme. Moderate hypofractionated radiotherapy has become routine practice for a selected population of patients treated for early-stage breast cancer. In April 2020, the Fast Forward (FF) study was published which introduced another extreme hypofractionated radiotherapy regimen in five sessions over a week. The aim of this work is to evaluate the population of first patients in whom this regimen was used in our department, as well as the results in terms of early toxicity. We retrospectively analysed all the patients treated in our department according to the Fast Forward protocol after establishing an institutional consensus regarding the selection of patients with breast cancer without indication for lymph node irradiation. All patients received breast-only irradiation at a total dose of 26 Gy in five fractions according to protocol. All patients were treated by modern conformational techniques with planning large volume coverage between 95 and 100%. Acute toxicity of the treatment was assessed using the NCI CTC v4.0 scale and the general condition was assessed according to the WHO classification. Between August 2020 and May 2021, 30 patients were included, treated on the breast alone without complement on the tumour bed or irradiation of the lymph node areas. The median age of the patients was 80 years (range: 60–85 years) with performance status 2 in 27 cases (89%). Only one patient had metastatic disease (3%), one patient presented locally advanced and 28 (94%) patients had early stage disease. Three patients (10%) were treated in dorsal decubitus according to the "field in the field" technique and 27 patients (90%) in isocentric lateral decubitus, which made it possible to avoid the organs at risk such as the heart (average dose of less than 1 Gy) and the lungs. The early toxicity observed was grade I radio dermatitis in 8 patients (27%). No grade 2 and 3 toxicity, as well as radiation-induced pain or lymphedema were observed. The results of this series of patients treated with hypofractionated radiotherapy according to the Fast Forward protocol on the breast alone with adapted techniques show that the protocol is feasible, with little early toxicity but a greater follow-up is necessary to assess long-term toxicity. [ABSTRACT FROM AUTHOR]

• A semi-automatic technique for whole breast RT with tangential IMRT fields was set. • The technique was validated on a sample of 60 patients against manual clinical 3DCRT. • AutoIMRT was shown to improve PTV coverage and homogeneity. • No relevant differences in doses to OARs were observed. • AutoIMRT plans were shown to be robust toward isocenter displacements. To implement a semi-automatic planning technique for whole breast irradiation with two tangential IMRT fields and to test the produced dose distribution against clinical 3DCRT plans, for introducing the technique in clinical practice. The Auto-Planning module of the Pinnacle3 (Philips) treatment planning system was used for generating a Treatment Technique on left-sided breast cancer patients treated in free breathing or in deep inspiration breath hold (DIBH) and to right-sided breast cancer patients. The technique was evaluated against 3DCRT clinical plans in terms of dosimetric plan parameters. Plan robustness toward patient displacements was assessed on a subset of patients by inducing shifts to the isocenter. A statistically significant improvement in target coverage and dose homogeneity was observed for autoIMRT. No statistically significant differences were observed for ipsilateral organs, except for the ipsilateral lung in left DIBH, where slightly lower D mean and V 18% are registered for autoIMRT. Slightly higher D mean doses (although far below the constraints) to contralateral organs were observed for autoIMRT plans. AutoIMRT plans were shown to be as robust as 3DCRT plans toward isocenter shifts, with a maximum decrease in CTV coverage of −2.2% and −2.1% for autoIMRT and 3DCRT, respectively. Average planning times were 40 min for 3DCRT and 6 min for IMRT plans. The developed autoIMRT technique was proven to be advantageous for target coverage and homogeneity and sufficiently robust towards isocenter displacements. The use of automated planning consistently reduces the planning workload with improvements in plan quality. [ABSTRACT FROM AUTHOR]

Simple Summary: Intraoperative electron radiation therapy (IOERT) has repeatedly demonstrated its power to yield high local control rates in all risk constellation of patients with invasive breast cancer when given as tumor bed boost prior to conventional whole breast irradiation (WBI) after breast conserving surgery (BCS). Since the standard for WBI continuously moved towards hypofractionation, we initiated a prospective trial in 2011 where we combined a high precision IOERT boost with a "moderate" hypofractionation schedule (15 × 2.7 Gy), the HIOB-trial [NCT01343459], as clinical evidence for this combination was scarce. Our results demonstrated a low five-year local recurrence rate (overall two events in a population of 1119 patients), which undershot such best evidences in two age groups (41–50 y and >50 y). As acute and late toxicity were mild with no impaired cosmetic outcome, the HIOB-concept seems to be a viable treatment option for patients who underwent BCS and intended WBI. Background and purpose: To investigate intraoperative electron radiation therapy (IOERT) as a tumor bed boost during breast conserving surgery (BCS) followed by hypofractionated whole breast irradiation (HWBI) on age-correlated in-breast recurrence (IBR) rates in patients with low- to high-risk invasive breast cancer. Material and methods: BCS and IOERT (11.1 Gy) preceded a HWBI (40.5 Gy) in 15 fractions. Five-year IBR-rates were compared by a sequential ratio test (SQRT) with best evidences in three age groups (35–40 y and 41–50 y: 3.6%, >50 y: 2%) in a prospective single arm design. Null hypothesis (H0) was defined to undershoot these benchmarks for proof of superiority. Results: Of 1445 enrolled patients, 326 met exclusion criteria, leaving 1119 as eligible for analysis. After a median follow-up of 50 months (range 0.7–104), we detected two local recurrences, both in the age group >50 y. With no observed IBR, superiority was demonstrated for the patient groups 41–50 and >50 y, respectively. For the youngest group (35–40 y), no appropriate statistical evaluation was yet possible due to insufficient recruitment. Conclusions: In terms of five-year IBR-rates, Boost-IOERT followed by HWBI has been demonstrated to be superior in patients older than 50 and in the age group 41–50 when compared to best published evidence until 2010. [ABSTRACT FROM AUTHOR]

Background: The most common secondary cancer is contralateral breast (CLB) cancer after whole breast irradiation (WBI). The aim of this study was to quantify the reduction of CLB dose in tangential intensity modulated radiotherapy (t-IMRT) for WBI using flattening-filter-free (FFF) beams. Materials and methods: We generated automated planning of 20 young breast cancer patients with limited user interaction. Dose-volume histograms of the planning target volume (PTV), ipsilateral lung, heart, and CLB were calculated. The dose of PTV, the most medial CLB point, and the CLB point below the nipple was measured using an ionization chamber inserted in a slab phantom. We compared the two t-IMRT plans generated by FFF beams and flattening-filter (FF) beams. Results: All plans were clinically acceptable. There was no difference in the conformal index, the homogeneity for FFF was significantly worse. For the ipsilateral lung, the maximum dose (Dmax) was significantly higher; however, V20 showed a tendency to be lower in the FFF plan. No differences were found in the Dmax and V30 to the heart of the left breast cancer. FF planning showed significantly lower Dmax and mean dose to the CLB. In contrast to the calculation results, the measured dose of the most medial CLB point and the CLB point below the nipple were significantly lower in FFF mode than in FF mode, with mean reductions of 21.1% and 20%, respectively. Conclusions: T-IMRT planning using FFF reduced the measured out-of-field dose of the most medial CLB point and the CLB point below the nipple. [ABSTRACT FROM AUTHOR]

Background: To implement a tangential treatment technique for whole breast irradiation using the Varian Halcyon and to compare it with Elekta Synergy Agility plans.Methods: For 20 patients two comparable treatment plans with respect to dose coverage and normal tissue sparing were generated. Tangential field-in-field treatment plans (Pinnacle/Synergy) were replanned using the sliding window technique (Eclipse/Halcyon). Plan specific QA was performed using the portal Dosimetry and the ArcCHECK phantom. Imaging and treatment dose were evaluated for treatment delivery on both systems using a modified CIRS Phantom.Results: The mean number of monitor units for a fraction dose of 2.67 Gy was 515 MUs and 260 MUs for Halcyon and Synergy Agility plans, respectively. The homogeneity index and dose coverage were similar for both treatment units. The plan specific QA showed good agreement between measured and calculated plans. All Halcyon plans passed portal dosimetry QA (3%/2 mm) with 100% points passing and ArcCheck QA (3%/2 mm) with 99.5%. Measurement of the cumulated treatment and imaging dose with the CIRS phantom resulted in lower dose to the contralateral breast for the Halcyon plans.Conclusions: For the Varian Halcyon a plan quality similar to the Elekta Synergy device was achieved. For the Halcyon plans the dose contribution from the treatment fields to the contralateral breast was even lower due to less interleaf transmission of the Halcyon MLC and a lower contribution of scattered dose from the collimator system. [ABSTRACT FROM AUTHOR]

This study aims to implement three-dimensional convolutional neural networks (3D-CNN) for clinical target volume (CTV) segmentation for whole breast irradiation and investigate the focus of 3D-CNNs during decision-making using gradient-weighted class activation mapping (Grad-CAM). A 3D-UNet CNN was adopted to conduct automatic segmentation of the CTV for breast cancer. The 3D-UNet was trained using three datasets of left-, right-, and both left- and right-sided breast cancer patients. Segmentation accuracy was evaluated using the Dice similarity coefficient (DSC). Grad-CAM was applied to trained CNNs. The DSCs for the datasets of the left-, right-, and both left- and right-sided breasts were on an average 0.88, 0.89, and 0.85, respectively. The Grad-CAM heatmaps showed that the 3D-UNet used for segmentation determined the CTV region from the target-side breast tissue and by referring to the opposite-side breast. Although the size of the dataset was limited, DSC ≥ 0.85 was achieved for the segmentation of breast CTV using the 3D-UNet. Grad-CAM indicates the applicable scope and limitations of using a CNN by indicating the focus of such networks during decision-making. [ABSTRACT FROM AUTHOR]

Purpose: To use cone-beam computed tomography (CBCT) imaging to determine the impacts of patient characteristics on the magnitude of geometric setup errors and obtain patient-specific planning target volume (PTV) margins from the correlated patient characteristics in whole breast irradiation (WBI).Methods: Between January 2019 and December 2019, a total of 97 patients who underwent breast-conserving surgery, followed by intensity-modulated radiation therapy in WBI, were scanned with pre-treatment CBCT for the first three treatment fractions and weekly for the subsequent fractions. Setup errors in the left-right (LR), superior-inferior (SI) and anterior-posterior (AP) directions were recorded and analyzed with patient characteristics-including age, tumor location, body mass index (BMI), chest circumference (CC) and breast volume (BV)-to examine the predictors for setup errors and obtain specific PTV margins.Results: A total of 679 CBCT images from 97 patients were acquired for analysis. The mean setup errors for the whole group were 2.32 ± 1.21 mm, 3.71 ± 2.21 mm and 2.75 ± 1.56 mm in the LR, SI and AP directions, respectively. Patients' BMI, CC and BV were moderately associated with setup errors, especially in the SI directions (R = 0.40, 0.43 and 0.22, respectively). Setup errors in the SI directions for patients with BMI > 23.8 kg/m2, CC > 89 cm and BV > 657 cm3 were 4.56 ± 2.59 mm, 4.77 ± 2.42 mm and 4.30 ± 2.43 mm, respectively, which were significantly greater than those of patients with BMI ≤ 23.8 kg/m2, CC ≤ 89 cm and BV ≤ 657 cm3 (P < 0.05). Correspondingly, the calculated PTV margins in patients with BMI > 23.8 kg/m2, CC > 89 cm and BV > 657 cm3 were 4.25/7.95/4.93 mm, 4.37/7.66/5.24 mm and 4.22/7.54/5.29 mm in the LR/SI/AP directions, respectively, compared with 3.64/4.64/5.09 mm, 3.31/4.50/4.82 mm and 3.29/5.74/4.73 mm for BMI ≤ 23.8 kg/m2, CC ≤ 89 cm and BV ≤ 657 cm3, respectively.Conclusions: The magnitude of geometric setup errors was moderately correlated with BMI, CC and BV. It was recommended to set patient-specific PTV margins according to patient characteristics in the absence of daily image-guided treatment setup. [ABSTRACT FROM AUTHOR]

Abstract Background This study aimed to evaluate the impact of previous local treatment on lymphatic drainage patterns in ipsilateral breast tumor recurrence (IBTR) based on our data on re-operative sentinel lymph node biopsy (re-SLNB) for IBTR. Methods Between April 2005 and December 2016, re-SLNB using lymphoscintigraphy with Tc-99 m phytate was performed in 136 patients with cN0 IBTR. Patients were categorized into two groups: the AX group included 55 patients with previous axillary lymph node dissection; the non-AX group included 69 patients with previous SLNB and 12 patients with no axillary surgery. The whole breast irradiation (RT) after initial surgery had performed in 17 patients in the AX group and 27 patients in the non-AX group. Results Lymphatic drainage was visualized in 80% of the AX group and 95% of the non-AX group (P

Purpose: This study aims to compare the dosimetric differences in intensity-modulated proton therapy (IMPT) using pencil beam scanning technology and intensity-modulated photon-based radiotherapy (IMRT) in hypofractionated whole-breast irradiation (HF-WBI) and find out the more beneficial technique. Methods and Materials: Eight breast cancer (BC) patients with pathological stage T1 ~ 2N0M0 were immobilized and underwent 4D-CT scanning used deep inspiration breath-hold (DIBH) technology. The IMPT and IMRT plans were designed for each patient. The IMPT plans used two en-face beam angles. IMRT plans were designed using the field in field technique. The optimization constraints of the two types of plans were identical. Prescription dose and regimen was 40.05 Gy (relative biological effect [RBE])/15 fx with a 10 Gy (RBE)/5 fx boost, five fractions a week. A dose of 95% of the target volume should not be less than the prescribed dose. The target coverage was evaluated using D1, D2, D50, D95, D98, and D99. The target dose distribution and conformity were evaluated using the Conformity index (CI) and the homogeneity index (HI). The Organs at risk (OARs) were evaluated using mean dose (Dmean) and maximum dose (Dmax). Ipsilateral Lung and Contralateral Lung were evaluated additionally using V5, V10, V20, V30. Results: The mean dose (Dmean) of the Heart (P = 0.012), Ipsilateral Lung (P = 0.036), Contralateral Lung (P = 0.012), and Spinal Cord (P = 0.012) were significantly reduced in IMPT plans. The IMPT also showed a tendency to reduce the V20 (P = 0.05) and V30 (P = 0.05) of the Ipsilateral Lung. But there was no significant difference in target coverage, homogeneity, and conformity between the IMRT and IMPT plans. Conclusion: Compared to IMRT, the IMPT using pencil beam scanning technology can spare OARs without compromising target coverage in BC patients undergoing HF-WBI, which potentially reduce the incidence of radiation-related adverse effects and thus may positively impact long-term survival. [ABSTRACT FROM AUTHOR]

Introduction: Controversy exists regarding potential increased toxic effects in patients with cosmetic implant-based augmentation (CIBA) who receive radiation therapy. We evaluated acute and chronic toxic effects associated with radiation therapy in women with prior CIBA treated with whole-breast irradiation (WBI) as part of breast conserving therapy (BCT) and compared these results against a cohort of patients without prior breast augmentation who received similar therapy., Methods: A retrospective review was performed to identify patients with a prior history of CIBA who subsequently underwent BCT with WBI. The control group consisted of consecutively treated patients without prior CIBA who also underwent BCT with WBI. Analyses included a comparison of baseline and treatment-associated factors between the augmentation and control groups, evaluation of toxic effects between both groups, and multivariable analysis of factors associated with the receipt of additional surgery following radiation., Results: Thirty-six patients with prior CIBA and 135 consecutively treated patients without CIBA were identified. Patients with prior CIBA were treated from 2006 through 2019, and patients without CIBA were treated from 2016 through 2019, though treatment characteristics and median follow-up time were similar between the two groups. Patients with prior CIBA were significantly less likely to experience acute moist desquamation (0% vs. 18%; P = .005). There were otherwise no statistically significant differences in acute (≤ 6 months) or chronic (> 6 months) toxic effects between the two groups. Rates of excellent/good chronic cosmetic outcome were 89% for the CIBA group and 97% in the control group (P = .094). On multivariable analysis, patients without prior CIBA (OR = 0.04; CI = 0.01-0.13; P < .001) and patients treated with moderately hypofractionated irradiation (OR = 0.08; CI = 0.02-0.23; P < .001) were significantly less likely to undergo additional surgery following receipt of WBI. Two patients experienced implant loss following radiation therapy., Conclusions: WBI as part of BCT in patients with prior implant-based breast augmentation appears safe and is associated with favorable cosmetic outcomes. There was an increased need for additional surgery in patients with prior CIBA, but rates of acute and chronic toxic effects appeared similar to those in nonaugmented patients., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We evaluate the combined usage of two systems, the Integral Quality Monitor (IQM) transmission detector and SoftDiso software, for in vivo dose monitoring by simultaneous detection of delivery and patient setup errors in whole breast irradiation. An Alderson RANDO phantom was adapted with silicon breast prostheses to mimic the female anatomy. Plans with simulated delivery errors were created from a reference left breast plan, and patient setup errors were simulated by moving the phantom. Deviations from reference values recorded by both monitoring systems were measured for all plans and phantom positions. A 2D global gamma analysis was performed in SoftDiso for all phantom displacements. Both IQM signals and SoftDiso R-values are sensitive to small MU variations. However, only IQM is sensitive to jaw position variations. Conversely, IQM is unable to detect patient positioning errors, and the R-value has good sensitivity to phantom displacements. A gamma comparison analysis allows one to determine alert thresholds to detect phantom shifts or relatively large rotations. The combined use of the IQM and SoftDiso allows for fast identification of both delivery and setup errors and substantially reduces the impact of error identification and correction on the treatment workflow. [ABSTRACT FROM AUTHOR]

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. • Whole breast irradiation (WBI) significantly improves 10-year local control and disease-free survival in patients with low-risk breast cancer. • The omission of WBI and tumour grading were negative predictors for local recurrence–free survival. • The benefit of WBI in terms of disease-free survival was not seen after axillary node dissection. • No RT effect was detected for overall survival after ten years. • For RT de-escalation, biological risk classifications have to be further evaluated. [ABSTRACT FROM AUTHOR]

Irradiating a tumor bed with boost dose after whole breast irradiation helps reducing the probability of local recurrence. However, the success of electron beam treatment with a small area aiming to cover a superficial lesion is a dual challenge as it requires an adequate dosimetry beside a double check for dose coverage with an estimation of various combined uncertainty of tumor location and losing lateral electron equilibrium within small field dimensions. this work aims to measure the electron beam fluence within different field dimensions and the deviation from measurement performed in standard square electron applicator beam flatness and symmetry, then to calculate the average range of the correction factor required to overcome the loss of lateral electron equilibrium. the electron beam used in this work generated from the linear accelerator model ELEKTA Precise and dosimetry system used were a pair of PTW Pin Point ion chambers for electron beam dosimetry at standard conditions and assessment of beam quality at a reference depth of measurement, with an automatic water phantom, then a Roos ion chamber was used for absolute dose measurement, and PTW 2Darray to investigate the beam fluence of four applicators 6, 10, 14 and 20 cm2 and 4 rectangular cutouts 6 × 14, 8 × 14, 6 × 17 and 8 × 17 cm2, the second part was clinical application which was performed in a precise treatment planning system and examined boost dose after whole breast irradiation. revealed that lower energy (6MeV and 8MeV) showed the loss of lateral electron equilibrium and deviation from measurements of a standard applicator more than the high energy (15 MeV) which indicated that the treatment of superficial dose with 6MeV required higher monitor unit to allow for the loss of lateral electron equilibrium and higher margin as well. [ABSTRACT FROM AUTHOR]

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 < 0.001). Conclusion: An automated treatment planning process can make the planning process efficient with improved plan quality. [ABSTRACT FROM AUTHOR]

Managing elderly breast cancer patients brings challenges both to physicians and patients themselves. There are certain controversial issues regarding local treatment of early breast cancer in this population. Since elderly patients are more likely to have comorbidities and functional limitations, they are more prone to undertreatment. Although surgical treatment in elderly patients were reported to be safe, severity and number of comorbidities are shown to be related with increased complications, hence may lead to higher mortality and lower life quality. Therefore, frailty is one of the concerns which prevents elderly patients to receive standard-of-care local treatment. Nevertheless, breast cancers developing in elderly are more likely to be low grade and luminal type. Until now, primary endocrine treatment without surgical resection, omitting whole breast irradiation after partial mastectomy and avoiding sentinel lymph node biopsy, which are otherwise accepted as standard-of-care, were questionned in healthy, low-risk, elderly fit patients. Two main issues were suggested to be considered when assessing the impact of local treatment options in this patient group; the clinical significance of treatments' effects, and the patients' expectations. Due to their vulnerability, baseline geriatric assessment should be the initial step for management in elderly breast cancer patients. Even in those who are healthy and fit with long life-expectancy, de-escalation in management might be an option in low-risk patients after considering patients' individual expectations and limited clinical benefits of standard local treatment options. [ABSTRACT FROM AUTHOR]

Purpose : The GEC-ESTRO has reported the equivalent outcomes of partial breast irradiation (PBI) using multicatheter interstitial brachytherapy (MCB) to whole breast irradiation (WBI) in breast-conserving therapy (BCT). We performed single-stage BCT with partial breast brachytherapy by intraoperative catheter placement. After the categorization of patients into inclusion and exclusion criteria on this trial, our databases were evaluated in order to translate it to Japanese patients. Material and methods : Patients undergoing BCT were retrospectively examined between November 2007 and December 2015. The technique is an open-cavity implant with a dose of 32 Gy in 8 fractions. The 4-year clinical outcomes of MCB-PBI were evaluated in the 2 distinct categories, and the comparison of the outcomes of MCB-PBI with WBI was performed in patients with unfavorable features. Results : Of a total of 501 lesions undergoing BCT, 301 lesions were treated with MCB-PBI and 200 lesions with WBI. At the median follow-up time of 52 months, the 4-year rate of ipsilateral breast tumor recurrence (IBTR)-free, disease-free (DFS), and overall survival (OS) in patients with MCB-PBI and WBI were 98.9% vs. 98.0% (p = 0.56), 97.0% vs. 95.3% (p = 0.78), and 99.6% vs. 98.2% (p = 0.38), respectively. Although in exclusion cohort treated with MCB-PBI, IBTR-free, and disease-free survival were significantly worse than in inclusion cohort, non-significantly worse outcomes was demonstrated than in exclusion cohort with WBI; IBTR-free survival (95.0% vs. 97.2%, p = 0.24), and disease-free survival (95.0% vs. 95.8%, p = 0.31). Conclusions : Single-stage BCT using MCB-PBI offered similar tumor control rates compering to WBI. However, further research is needed to define the benefit for patients with an exclusion criteria.

This study demonstrated the feasibility and advantages of a hybrid, volumetric arc therapy technique that used two 90° coplanar arcs and two three-dimensional conformal tangential beams in the simultaneous-integrated boost radiotherapy of left-sided breast cancer after breast-conserving surgery. A total of nine patients with stage I, left-sided breast cancer who underwent breast-conserving surgery were selected for this retrospective study. For each patient, a hybrid arc plan was generated and then compared with two hybrid intensity-modulated radiotherapy plans. All plans were optimized using the same objectives and dose constraints. The prescription dose was 50.4 Gy to the planning target volume with simultaneous boost to 60 Gy to the expanded gross target volume in 28 fractions. The differences among these hybrid plans were analyzed by the Kolmogorov–Smirnov test or the Wilcoxon rank sum test. The hybrid arc plans achieved the clinical requirements of target dose coverage and normal tissue (NT) dose constraints. It was found that the hybrid arc plans showed advantages in the conformity index of the expanded gross target volume, the V5of the heart, the D2of the left ventricle, and the D2and V50.4of NTs. The average beam-on time and monitor units of the hybrid arc plans were significantly lower (P < 0.001).

Purpose: There is uncertainty about outcomes differences between partial breast irradiation (PBI) and whole breast irradiation (WBI) for early-stage breast cancer. Methods: Prospective randomized trials comparing adjuvant PBI to WBI in early-stage invasive breast cancer were identified using PubMed. Odds ratios (OR), 95% confidence intervals and absolute risks were computed for pre-specified efficacy and toxicity outcomes including cosmesis. Subgroup analysis evaluated the effect of PBI modality (external beam radiation treatment [EBRT], intraoperative radiation treatment [IORT] or brachytherapy) on efficacy. Meta-regression analysis explored the influence of median follow-up, patient and tumor characteristics on results. Results: Nine trials comprising 14514 patients were included. While PBI was associated with increased odds of local recurrence compared to WBI (OR 1.69, P < 0.001), it was associated with reduced odds of death without breast cancer recurrence (OR 0.55, P < 0.001) and with improvement in overall survival (OS) that approached, but did not meet statistical significance (OR 0.84, P = 0.06). Subgroup analysis for PBI modality showed significant differences in the odds of local recurrence, based on method of PBI with EBRT showing the lowest magnitude of inferiority. Nodal involvement was associated with higher local recurrence risk, while larger tumors were associated with lesser improvement in death without breast cancer recurrence and OS. PBI was associated with higher odds of fat necrosis (OR 1.72, P = 0.002). Worse cosmetic outcome with PBI approached statistical significance (OR 1.23, P = 0.06). Conclusions: Compared to WBI, PBI is associated with higher odds for local recurrence and toxicity, but less death without breast cancer recurrence. The balance between benefit and risk of PBI appears optimal for women with smaller hormone receptor positive tumors, without nodal involvement and treated with EBRT. [ABSTRACT FROM AUTHOR]

Following breast conserving surgery, the standard of care has been to deliver adjuvant radiation therapy directed to the whole breast (WBI) over a period of 3‐7 weeks. Over the past decade, increasing data have supported the concept that treatment to the whole breast may not be required in selected patients, allowing for the emergence of partial breast irradiation (PBI). Multiple randomized trials with 5‐10 years of follow‐up have been published documenting the safety and efficacy associated with PBI using multiple techniques. Questions that remain to be answered include (a) what is the optimal PBI technique for each clinical scenario, (b) are there additional patients that can be effectively managed with PBI approaches, and (c) are there different techniques/dose schedules that allow for further reduction in treatment duration and/or toxicities? Partial breast irradiation represents a standard approach for appropriately selected patients. PBI provides comparable clinical outcomes to WBI while allowing for a reduction in the duration treatment and the potential for reduced toxicities. Future studies may also help to better define which patients require no radiation, PBI, hypofractionated WBI or conventional WBI, based upon patient, clinical, pathologic features as well as potentially using tumor genetics. [ABSTRACT FROM AUTHOR]

Abstract Purpose Since accelerated partial breast irradiation has demonstrated non-inferiority to whole breast irradiation regarding recurrence rate in patients with early stage breast cancer, our objective was to compare its impact on short-term adverse events, patient satisfaction and costs. Materials and methods Patients with early stage breast cancer treated by breast-conserving surgery between 2007 and 2012 were included: 48 women who received three-dimensional conformal accelerated partial breast irradiation in a multicentre phase-II trial were paired with 48 patients prospectively treated with whole breast irradiation. Adverse events, and patients' opinions concerning cosmesis, satisfaction and pain, were gathered 1 month after treatment. Direct and indirect costs were collected from the French National Health Insurance System perspective until the end of radiotherapy. Results When comparing its impact, skin reactions occurred in 37% of patients receiving three-dimensional conformal accelerated partial breast radiotherapy and 60% of patients receiving whole breast irradiation (P = 0.07); 98% were very satisfied in the group three-dimensional conformal accelerated partial breast radiotherapy versus 46% in the group treated with whole breast irradiation (P < 0.001); direct costs were significantly lower in the group treated with partial breast irradiation (mean cost: 2510 € versus 5479 €/patient), due to less radiation sessions. Conclusion In patients with early-stage breast cancer, partial irradiation offered a good alternative to whole breast irradiation, as it was less expensive and satisfactory. These, and the clinical safety and tolerance results, need to be confirmed by long-term accelerated partial breast irradiation results in on-going phase III trials. [ABSTRACT FROM AUTHOR]

Background: There are concerns regarding local toxicity when IORT is applied in Asian women with a smaller breast volume than that of Western women. Trials are required to develop safety profiles for this technique. The aim of this trial was to evaluate acute toxicity after intra-operative radiotherapy (IORT) with low-energy X-ray plus whole breast irradiation (WBI) in Asian patients with breast cancer.Methods: This single-arm, single-institute, phase II trial investigated acute toxicity after completion of radiotherapy (targeted IORT followed by WBI) in Korean patients treated with breast-conserving surgery (BCS). In the conventional WBI arm from the TARGIT-A trial, the incidence of acute toxicity within 6 months was 15%. To prove the non-inferiority of the acute toxicity rate, 215 patients were required. This trial is registered with ClinicalTrials.gov (NCT02213991).Results: Two-hundred and fifteen women were enrolled, and 198 underwent IORT. In 33 patients, clinically significant complications during the acute period were noted. The incidence of acute toxicity was 16.7% (95% CI 11.5-21.9%). There were 29 patients with seroma needing more than 3 aspirations, 4 with wound infection, and 2 with skin breakdown. There was no difference in the rate of complications according to the tumor volume or the tumor-breast volume ratio. Advanced age and high BMI were risk factors for acute complications.Conclusions: Targeted intra-operative radiotherapy using Intrabeam® is a safe procedure for Korean patients with breast cancer with an acceptable toxicity profile in the acute period. [ABSTRACT FROM AUTHOR]

Abstract Introduction The aims of this study were to investigate the correlation between lymphatic drainage and the sentinel lymph node (SLN) status of the subregions in the context of the clinic-pathological parameters of the tumour and the coverage of the axillary volumes by standard and high tangential fields (STgF and HTgF) for whole breast radiotherapy and axillary reverse mapping (ARM). Patients and methods 933 women with early breast cancer and clinically negative axillary status underwent breast surgery and SLN biopsy followed by axillary lymph node dissection in SLN-positive cases. The subregional localisation of the SLN(s) was registered and statistically analysed with the clinic-pathological characteristics of the breast tumour. In node-positive patients treated with breast-conserving therapy in whom the SLNs were found in the anterior or posterior axillary subregions, the axillary volumes were contoured using the Radiation Therapy Oncology Group contouring atlas (n = 61). Results In 91.1% (n = 797) of the cases, the SLN appeared in the anterior, posterior or central subregions. Using HTgF, Level I or II were completely covered in 65.6% (40/61) and 6.6% (4/61) of the cases, respectively. With STgF, the complete coverage was 0% for both levels. 6.8% (n = 63) of all cases had one positive lymph node in the expected ARM lymph node regions. Discussion A SLN is more than likely to be present in the anterior, posterior and central axillary subregions. Tangential fields allow only limited coverage of the axillary volumes. Preserving the lateral subregion during ARM may increase the possibility of understaging. [ABSTRACT FROM AUTHOR]