Adjuvant Hypofractionated Whole Breast Irradiation (WBI) vs. Accelerated Partial Breast Irradiation (APBI) in Postmenopausal Women with Early Stage Breast Cancer: 5Years Update of the HYPAB Trial.

Therapeutical strategies in breast cancer are continuously updating. Recent researches assessed the possibility of irradiating only the surgical bed in selected patients (Partial Breast Irradiation, PBI). In 2014 we designed a study to evaluate toxicity and cosmesis of APBI using Volumetric Modulated Arc Therapy-Rapid Arc compared with hypofractionated whole breast irradiation (WBI). We present here the 5-years updated data. HYPAB was a single-institution randomized trial that recruited 172 patients from 2015 to 2018. Patients underwent conserving surgery and were randomized to either adjuvant WBI (40.5Gy/15 fractions with simultaneous boost to 48 Gy to tumoral bed) or APBI (30Gy/5 fractions), both delivered with VMAT-RA technique. Clinical evaluation was performed during the first visit, once a week during radiotherapy and during follow up. Cosmesis was assessed using the Harvard Scale for Breast Cosmesis. At the time of the analysis 161 patients were eligible, 53% in the WBI and 47% in the APBI group, with a median follow-up of 67 months. Most common late skin toxicities were G1 fibrosis (32%) and oedema (28%) and were higher in the WBI group; no G3 toxicities were observed. Cosmesis was rated poor in only 6 cases. 147 patients had no evidence of disease at the last follow-up, and no patients died of the disease. Mature results confirm the safety and efficacy of APBI in selected early stage breast cancer patients. Late toxicity is improved in the APBI arm at the cost of a slight increase in local relapse. Further studies are ongoing to better elucidate the use of APBI as a de-escalation approach.

Accelerated Partial Breast Irradiation Using 5 Daily Fractions: A Prospective, Phase 2, Multicenter Trial of Cosmetic Outcomes and Toxicity-ACCEL Final Results.

PURPOSE: This study investigated the cosmetic degradation and toxicity for an accelerated partial breast irradiation (APBI) prescription delivered in 5 fractions over 1 week and compared the outcomes with those of whole breast irradiation (WBI). METHODS AND MATERIALS: The trial was a multicenter, single-arm, phase 2 prospective cohort study. Eligible women 50 years of age or older with estrogen receptor-positive and human epidermal growth factor receptor 2-negative invasive ductal carcinoma or ductal carcinoma in situ after breast-conserving surgery received 27 Gy in 5 daily fractions of APBI. The primary endpoint was noninferiority of 2-year cosmesis using the RAPID trial's WBI arm as the control arm. A global consensus cosmetic score using a European Organisation for Research and Treatment of Cancer rating scale score of excellent, good, fair, or poor for each patient at baseline and 2 years was generated by a panel of 5 radiation oncologists using photographs of treated and untreated breasts. RESULTS: From 2016 to 2019, 298 eligible women were enrolled. By the 2-year follow-up, 76 patients had been lost or withdrawn and 3 had died, resulting in 219 patients available for complete, 2-year photographic cosmetic evaluation. The median follow-up for all participants was 4.7 years (IQR, 3.8-5.5 years). No patient had a fair or poor cosmetic score at the 2-year evaluation. Cosmesis was better or unchanged for 97% of patients and worse for 3% (excellent to good), and no cosmetic failures occurred. The confidence intervals were 0.88 (0.86-0.90) and 1.00 (0.99-1.00) for the RAPID and ACCEL trials, respectively. CONCLUSIONS: Cosmetic degradation with 5 daily treatments of the ACCEL trial's APBI intervention is noninferior to the WBI arm of the RAPID trial.

Accelerated Partial Breast Irradiation for HER2-Positive Early-Stage Breast Cancer.

PURPOSE: HER2-positive (HER2+) breast cancer historically exhibited the most adverse local outcomes and, consequently, has had limited representation among trials of partial breast irradiation (PBI). We hypothesized that with contemporary HER2-targeted agents, patients may now exhibit excellent disease control outcomes after adjuvant PBI. METHODS AND MATERIALS: Using a prospectively maintained institutional database, we identified patients with HER2+ breast cancer treated with breast conserving surgery (BCS) and PBI from 2000 to 2022. Salient clinicopathologic and treatment parameters were collected. All patients received external beam PBI to 40 Gy in 10 daily fractions. Cumulative incidence functions were calculated to estimate the incidence of local recurrence (LR) with the competing risk of death. RESULTS: We identified 1248 patients who underwent PBI at our institution, of whom the study cohort comprised 52 (4%) with HER2+ breast cancer (median age, 64 years; range, 44-87). Nearly all had T1 tumors (98%; median size, 12 mm [range, 1-21 mm]). Most had estrogen receptor positive disease (88%), and all patients had negative surgical margins. Nearly all underwent sentinel node biopsy (94%), with the remainder undergoing no surgical axillary evaluation. Forty-two (81%) received chemotherapy; 40 (77%), hormone therapy; and 42 (81%), HER2-directed therapy, most commonly trastuzumab. At 143.8 person-years of follow-up (range, 7-226 months for each patient), we observed 2 LR events at 14 and 26 months, respectively, yielding a 2-year LR rate of 3.8%. No regional or distant recurrences were observed, nor were any breast-specific mortality events. Two deaths were observed, both without evidence of disease. CONCLUSIONS: Among a cohort of patients with HER2+ early-stage breast cancer managed with BCS and PBI, we observed a 2-year LR rate of 3.8%, with no regional or distant recurrences and excellent overall survival. These findings require confirmation with longer follow-up among larger cohorts but appear consistent with the excellent results of contemporary randomized trials of PBI unselected for HER2 status.

Large institutional experience of early outcomes and dosimetric findings with postoperative stereotactic partial breast irradiation in breast cancer.

PURPOSE: To analyze the dosimetric and toxicity outcomes of patients treated with postoperative stereotactic partial breast irradiation (S-PBI). METHODS: We identified 799 women who underwent S-PBI at our institution between January 2016 and December 2022. The most commonly used dose-fraction and technique were 30 Gy in 5 fractions (91.7 %) and a robotic stereotactic radiation system with real-time tracking (83.7 %). The primary endpoints were dosimetric parameters and radiation-related toxicities. For comparison, a control group undergoing ultra-hypofractionated whole breast irradiation (UF-WBI, n = 468) at the same institution was selected. RESULTS: A total of 815 breasts from 799 patients, with a median planning target volume (PTV) volume of 89.6 cm3, were treated with S-PBI. Treatment plans showed that the mean and maximum doses received by the PTV were 96.2 % and 104.8 % of the prescription dose, respectively. The volume of the ipsilateral breast that received 50 % of the prescription dose was 32.3 ± 8.9 %. The mean doses for the ipsilateral lung and heart were 2.5 ± 0.9 Gy and 0.65 ± 0.39 Gy, respectively. Acute toxicity occurred in 175 patients (21.5 %), predominantly of grade 1. Overall rate of late toxicity was 4 % with a median follow-up of 31.6 months. Compared to the UF-WBI group, the S-PBI group had comparably low acute toxicity (21.5 % vs. 25.2 %, p = 0.12) but significantly lower dosimetric parameters for all organs-at-risks (all p < 0.05). CONCLUSION: In this large cohort, S-PBI demonstrated favorable dosimetric and toxicity profiles. Considering the reduced radiation exposure to surrounding tissues, external beam PBI with advanced techniques should at least be considered over traditional WBI-based approaches for PBI candidates.

Cosmetic Outcome and Toxicity After Stereotactic Accelerated Partial Breast Irradiation in Early Breast Cancer: A Prospective Observational Cohort Study.

PURPOSE: The aim of this work was to prospectively evaluate the toxicity and cosmetic outcomes of 5-fraction, stereotactic, accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: This prospective observational cohort study enrolled women who underwent APBI for invasive carcinoma or carcinoma in situ of the breast. APBI was delivered using a CyberKnife M6 robotic radiosurgery system at 30 Gy in 5 nonconsecutive, once-daily fractions. Women undergoing whole breast irradiation (WBI) were also enrolled for comparison. Patient-reported and physician-assessed adverse events were recorded. Breast fibrosis was measured using a tissue compliance meter, and breast cosmesis was assessed using BCCT.core (an automatic, computer-based software). Outcomes were collected until 24 months posttreatment according to the study protocol. RESULTS: In total, 204 patients (APBI, n = 103; WBI, n = 101) were enrolled. Regarding patient-reported outcomes, the APBI group reported significantly less skin dryness (6.9% vs 18.3%; P = .015), radiation skin reaction (9.9% vs 23.5%; P = .010), and breast hardness (8.0% vs 20.4%; P = .011) at 6 months than the WBI group. On physician assessment, the APBI group had significantly less dermatitis at 12 months (1.0% vs 7.2%; P = .027) than the WBI group. Any severe toxicities after APBI were rare in patient-reported outcomes (score ≥3, 3.0%) and physician assessments (grade ≥3, 2.0%). In the uninvolved quadrants, measured fibrosis in the APBI group was significantly lower than that in the WBI group at 6 (P = .001) and 12 (P = .029) months but not at 24 months. In the involved quadrant, measured fibrosis in the APBI group was not significantly different from that in the WBI group at any time. Cosmetic outcomes in the APBI group were mostly excellent or good (77.6%) at 24 months, and there was no significant cosmetic detriment from the baseline. CONCLUSIONS: Stereotactic APBI was associated with less fibrosis in the uninvolved breast quadrants than WBI. Patients showed minimal toxicity and no detrimental effects on cosmesis after APBI.

Hypofractionated whole breast irradiation in association with hypofractionated or normofractionated boost to the tumor bed in early breast cancer: tolerance and efficacy analysis.

BACKGROUND: The boost to the tumor bed improves local control in breast cancer and it is an important part of the breast conserving therapy. However, information about the use of a hypofractionated boost is sparse, thus further studies are needed. We conducted a retrospective study with the aim of comparing hypofractionated boost (HB) and normofractionated boost (NB) on skin toxicity and local control. MATERIALS AND METHODS: A total of 96 women with early breast cancer undergoing breast-conserving surgery and hypofractionated whole breast irradiation (WBI) were retrospectively analyzed divided into hypofractionated boost group and conventional fractionation boost group. Forty-nine patients were treated with NB with 16 Gy in 8 fractions and 47 patients were treated with HB with 13.35 Gy in 5 fractions. We examined acute and chronic toxicity with CTCAE version 5. RESULTS: The median follow-up was 49.5 months (26-67). Median age was 57 years (36-82). Sixty-six patients (68.7%) were younger than 60 years at the time of boost and 30 (31.2%) were older than 60 years who received the boost due to poor prognostic factors. No differences were found between the two groups in terms of patient, tumor or treatment characteristics. Grade 2 acute skin toxicity was 6.3% in the NB group and 4.2% in the HB group. Chronic skin induration was 4.2% in the NB group and 1% in the HB group. They did not show grade 3 skin toxicity. There were also no differences in acute or late skin toxicity between the two groups. No local recurrences were evidenced. CONCLUSIONS: Hypofractionated WBI associated with HB treatment is a viable option in the management of conservative breast therapy given the good tolerance and similar local control.

Voluntary versus mechanically-induced deep inspiration breath-hold for left breast cancer: A randomized controlled trial.

BACKGROUND AND PURPOSE: Deep inspiration breath-hold (DIBH) protects critical organs-at-risk (OARs) for adjuvant breast radiotherapy. Guidance systems e.g. surface guided radiation therapy (SGRT) improve the positional breast reproducibility and stability during DIBH. In parallel, OARs sparing with DIBH is enhanced through different techniques e.g. prone position, continuous positive airway pressure (CPAP). By inducing repeated DIBH with the same level of positive pressure, mechanically-assisted and non-invasive ventilation (MANIV) could potentially combine these DIBH optimizations. MATERIALS AND METHODS: We conducted a randomized, open-label, multicenter and single-institution non-inferiority trial. Sixty-six patients eligible for adjuvant left whole-breast radiotherapy in supine position were equally assigned between mechanically-induced DIBH (MANIV-DIBH) and voluntary DIBH guided by SGRT (sDIBH). The co-primary endpoints were positional breast stability and reproducibility with a non-inferiority margin of 1 mm. Secondary endpoints were tolerance assessed daily via validated scales, treatment time, dose to OARs and their inter-fraction positional reproducibility. RESULTS: Differences between both arms for positional breast reproducibility and stability occurred at a sub-millimetric level (p < 0.001 for non-inferiority). The left anterior descending artery near-max dose (14,6 ± 12,0 Gy vs. 7,7 ± 7,1 Gy, p = 0,018) and mean dose (5,0 ± 3,5 Gy vs. 3,0 ± 2,0 Gy, p = 0,009) were improved with MANIV-DIBH. The same applied for the V5Gy of the left ventricle (2,4 ± 4,1 % vs. 0,8 ± 1,6 %, p = 0,001) as well as for the left lung V20Gy (11,4 ± 2,8 % vs. 9,7 ± 2,7 %, p = 0,019) and V30Gy (8,0 ± 2,6 % vs. 6,5 ± 2,3 %, p = 0,0018). Better heart's inter-fraction positional reproducibility was observed with MANIV-DIBH. Tolerance and treatment time were similar. CONCLUSION: Mechanical ventilation provides the same target irradiation accuracy as with SGRT while better protecting and repositioning OARs.

Development, implementation, and results of a simulation-based hands-on brachytherapy workshop for medical students.

PURPOSE: The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) require the development of competence-oriented teaching formats. In addition, there is a great need for high-quality teaching in the field of radiation oncology, which manifests itself already during medical school. For this reason, we developed a simulation-based, hands-on medical education format to teach competency in performing accelerated partial breast irradiation (APBI) with interstitial multicatheter brachytherapy for early breast cancer. In addition, we designed realistic breast models suitable for teaching both palpation of the female breast and implantation of brachytherapy catheters. METHODS: From June 2021 to July 2022, 70 medical students took part in the hands-on brachytherapy workshop. After a propaedeutic introduction, the participants simulated the implantation of single-lead catheters under supervision using the silicone-based breast models. Correct catheter placement was subsequently assessed by CT scans. Participants rated their skills before and after the workshop on a six-point Likert scale in a standardized questionnaire. RESULTS: Participants significantly improved their knowledge-based and practical skills on APBI in all items as assessed by a standardized questionnaire (mean sum score 42.4 before and 16.0 after the course, p < 0.001). The majority of respondents fully agreed that the workshop increased their interest in brachytherapy (mean 1.15, standard deviation [SD] 0.40 on the six-point Likert scale). The silicone-based breast model was found to be suitable for achieving the previously defined learning objectives (1.19, SD 0.47). The learning atmosphere and didactic quality were rated particularly well (mean 1.07, SD 0.26 and 1.13, SD 0.3 on the six-point Likert scale). CONCLUSION: The simulation-based medical education course for multicatheter brachytherapy can improve self-assessed technical competence. Residency programs should provide resources for this essential component of radiation oncology. This course is exemplary for the development of innovative practical and competence-based teaching formats to meet the current reforms in medical education.

Update on Accelerated Whole Breast Irradiation.

Since the advent of breast conservation, adjuvant radiation therapy (RT) has been standard of care following breast conserving surgery (BCS). Radiation therapy following BCS has traditionally been whole breast irradiation (WBI); studies comparing breast conservation to mastectomy utilized standard fractionation WBI, which delivers treatment daily over 5 to 7 weeks (1.8-2 Gy/fraction) and was the standard for decades. More recently, multiple randomized trials have compared standard fractionation WBI to moderately hypofractionated WBI (2.66 Gy/fraction, 15-16 fractions), which allows for completion of treatment in 3 to 4 weeks. Results have demonstrated no difference in local control between these two approaches with comparable toxicity and cosmetic outcomes with long-term follow-up. As such, moderately hypofractionated WBI represents the standard of care approach for most patients with early-stage breast cancer following BCS at this time. In the past few years, ultra-hypofractionated WBI (5.2-5.7 Gy/fraction, 5 fractions) has emerged with promising outcomes; 5-year outcomes from the FAST-Forward randomized trial demonstrated noninferiority between ultra-hypofractionated WBI and moderately hypofractionated WBI. Moving forward, long-term outcomes from ultra-hypofractionated WBI studies are expected, as well as the potential for incorporating moderately hypofractionated regimens into patients requiring regional nodal irradiation following BCS. Finally, the advent of ultra-short regimens may allow clinicians to re-evaluate treatment de-intensification in early-stage breast cancer to consider radiation therapy alone following BCS in lieu of endocrine therapy.

Breast brachytherapy: Building a bright future on the foundation of a rich history of advancement in technology, technique, and patient-centered care.

For over 20 years, the concept of accelerated partial breast irradiation (APBI) has received considerable attention. Initially concentrating on the appropriateness of APBI as an alternative treatment to whole breast radiotherapy, investigation and innovation evolved towards dose delivery and technique appropriateness. The purpose of this article is to review the pertinent literature that supports the role brachytherapy serves in delivering APBI and the recognized brachytherapy techniques for dose delivery. Publications establishing techniques utilizing multicatheter brachytherapy, single-entry brachytherapy applicators, permanent breast seed implantation brachytherapy, noninvasive breast brachytherapy and electronic brachytherapy are described. The use of brachytherapy for repeat breast conservation therapy is additionally reviewed. A historical perspective and potential direction of future investigation and innovation are presented.

Updates on the APBI-IMRT-Florence Trial (NCT02104895) Technique: From the Intensity Modulated Radiation Therapy Trial to the Volumetric Modulated Arc Therapy Clinical Practice.

Several phase 3 trials have demonstrated partial breast irradiation noninferiority compared with whole breast irradiation in terms of local control and similar or reduced toxicity. During recent years, especially owing to the COVID-19 pandemic, a growing interest in 5-fraction regimens emerged. The APBI-IMRT-Florence trial (NCT02104895) schedule (30 Gy in 5 fractions) might represent an appealing treatment option, being both a safe and effective partial breast irradiation schedule, with long-term reported results. The aim of this report is to support planners interested in implementing this technique and to warrant equal access to postoperative radiation treatment for most early breast cancer patient candidates. We report the current delivery technique optimized from the original protocol and the updated dose constraints for plan optimization. We also report a statistical analysis of dosimetric parameters on 50 patients treated in consecutive fractions. Treatment-related toxic effects were assessed using the acute radiation morbidity scoring criteria and late radiation morbidity scoring scheme from the Radiation Therapy Oncology Group and the European Organisation for Research and Treatment of Cancer. The mean volume of ipsilateral breast was 731 cm3 (standard deviation ± 450; range, 151-2205) and the mean planning target volume (PTV) was 139 cm3 (standard deviation ± 48; range, 55-259). There was good correlation between ipsilateral breast V15Gy and the ratio between the PTV and ipsilateral breast volume (R2 = .911). At a median follow-up of 4.5 years, 32% of patients (n = 16) developed any grade 1 acute toxic effect. No grade >1 toxic effect was observed. Sixteen percent of patients (n = 8) developed any grade 1 late toxic effect. No grade >1 toxic effect was observed. Physician-assessed cosmesis was reported as excellent (84%), good (14%), and fair (2%). The schedule of 30 Gy in 5 consecutive fractions might represent a safe, easy-to-deliver, and cost-effective option for appropriately selected patients affected by early breast cancer.

A Meta-Analysis of Trials of Partial Breast Irradiation.

PURPOSE: Partial breast irradiation (PBI) is the delivery of radiation therapy (RT) limited to the tumor bed after breast conserving surgery. The results of recent trials of PBI compared with whole breast irradiation (WBI) have suggested conflicting results with respect to local control and toxicity. The purpose of this meta-analysis was to assess effectiveness of PBI and to compare the different techniques. METHODS AND MATERIALS: A meta-analysis of aggregate data from published randomized trials was performed to examine the effectiveness of PBI compared with WBI in patients with invasive breast cancer and ductal carcinoma in situ. Relevant data were extracted. The primary outcome was any ipsilateral breast event (invasive or noninvasive). Secondary outcomes included acute and late toxicity. The results of randomized trials were pooled using a fixed effects model and the inverse variance method. RESULTS: Fifteen trials involving 16,474 patients were identified. The majority of enrolled patients were >60 years of age and had T1N0 grade 1 to 2 disease treated with hormone therapy. The percent of ipsilateral breast events was higher in patients treated with PBI compared with WBI (5.0% vs 2.8%; risk ratio [RR], 1.72; 95% confidence interval [CI], 1.47-2.02). Heterogeneity (P = .0002) was observed between the 4 PBI techniques: external beam RT without computed tomography (CT) planning (RR, 2.06; 95% CI, 1.36-3.12); brachytherapy (RR, 1.21; 95% CI, 0.65-2.25); intraoperative RT (RR, 2.79; 95% CI, 2.08-3.73); and external beam RT with CT planning (RR, 1.25; 95% CI, 0.99-1.58). When external beam RT without CT planning and intraoperative RT trials were excluded, the percent of ipsilateral breast events was 3.3% versus 2.6%, respectively (RR, 1.25; 95% CI, 1.00-1.55; P = .05), and no heterogeneity was observed (P = .92). Overall, acute toxicity was less with PBI, and the effect on late toxicity varied by technique. CONCLUSIONS: Overall, WBI was more effective than PBI, but the effectiveness of PBI was technique related. PBI was less effective when given by external beam RT without CT planning or intraoperative therapy. Although PBI given by multicatheter brachytherapy or external beam RT with CT planning tended to be statistically less effective than WBI, the absolute difference between groups for ipsilateral breast events was very small (<1%), supporting these approaches for women considering PBI.

Five Fraction External Beam Partial Breast Irradiation: A User's Guide.

OBJECTIVE: Mature follow up from multiple randomized trials have demonstrated the safety and efficacy of external beam partial breast irradiation (PBI) for appropriately selected patients with early stage breast cancer. Despite this evidence, external beam PBI remains underutilized. In this user guide we outline patient selection, workflow, and address possible challenges to aid in implementation of evidence-based external beam PBI. MATERIALS AND METHODS: Review of the current guidelines for PBI suitability, surgical considerations, treatment technique, simulation, contouring, and treatment planning, citing the latest published literature to support PBI utilization. RESULTS: Prospective data supports the use of 30 Gy in 5 fractions delivered with intensity modulated radiation therapy on a daily or every other day basis for a significant proportion of early stage breast cancer patients. The surgical cavity must be clearly visualized on treatment planning scan, recommend 3-5 weeks post-operatively, and the recommended clinical target volume expansion on the surgical cavity is 0.5-1.0 cm. A planning target volume expansion, based on motion management and image guidance, of 0.5-1.0 cm should be used. Organ at risk dose constraints of heart V3Gy ≤10% and contralateral breast Dmax ≤1 Gy are often achievable. CONCLUSIONS: Five fraction external beam PBI is a highly effective treatment with very limited toxicity for patients with early stage breast cancer following breast conserving surgery. Commonly utilized intensity modulated treatment planning techniques with plan delivery on standard linear accelerators results significant normal tissue sparing and makes implementation feasible at most radiation oncology centers.

Contralateral breast radiation doses in breast cancer patients treated with helical tomotherapy.

We aimed to evaluate contralateral breast doses calculated with a Treatment Planning System (TPS) and verified with metal oxide semiconductor field effect transistor (MOSFET) detectors in patients with early-stage breast cancer (BC) who received helical tomotherapy (HT) after breast-conserving surgery. The dosimetric data of 30 patients (15 left-sided and 15 right-sided) with BC treated with 50.4 Gy to the whole breast and 64.4 Gy to the tumor bed in 28 fractions were analyzed. TPS doses were calculated and MOSFET doses were measured in the contralateral breast (CB) at cranial, caudal, and midpoint and 2 cm lateral to the central point. TPS and MOSFET doses were compared in the entire cohort as well as by tumor location (inner vs outer quadrant) and planning target volume of the breast (<1200 cc vs ≥1200 cc). The average doses at superior, inferior, central, and lateral points calculated with the TPS were 0.26 ± 0.15 cGy, 0.21 ± 0.09 cGy, 0.65 ± 0.14 cGy, and 0.50 ± 0.11 cGy, respectively, and were 0.37 ± 0.16 cGy, 0.34 ± 0.12 cGy, 0.60 ± 0.18 cGy, and 0.34 ± 0.15 cGy, respectively in MOSFET readings. Except for the central point, TPS-calculated doses and MOSFET readings were differed. The doses to the CB in patients with inner and outer quadrant tumors were not significantly different. In patients with large breasts, MOSFET doses were higher at superior and lateral points than TPS doses, but TPS doses were greater at inferior points. MOSFET readings were higher than TPS calculated doses in patients with inner or outer quadrant tumors in small or large breast volumes. The dose calculated by the TPS and that measured by MOSFET differed by a very small amount. The maximum dose to the CB administered at the midpoint was 1.8 Gy, as calculated using the TPS and confirmed using MOSFET detectors, in patients with early-stage BC undergoing breast-only radiotherapy with HT.

Accelerated Partial Breast Irradiation: Florence Phase 3 Trial Experience and Future Perspectives.

Accelerated partial breast irradiation Florence phase 3 trial is a single-center study comparing intensity-modulated based accelerated partial breast irradiation (PBI, 30 Gy in 5 fractions) and whole breast irradiation (50 Gy in 25 fractions) followed by a tumor bed boost (10 Gy in 5 fractions). This easy-to-deliver PBI approach showed excellent long-term disease control with favorable safety and cosmetic outcome profiles. A plateau has been probably reached concerning the reduction of the number of fractions in the postoperative PBI setting. A 5-fraction schedule is the standard regimen and probably the appropriate compromise in terms of efficacy, safety, and quality of life, also considering the negative results of most intraoperative single-fraction PBI trials. A new frontier is now open on the potential benefit of preoperative PBI delivery, although concerns remain on the optimal dose, fractionation, and technique. Hereby we report the accelerated PBI Florence phase 3 trial experience and future perspectives.

EFFECT OF PELVIC LEAD SHIELD ON ORGAN DOSES IN POSTERO-ANTERIOR CHEST RADIOGRAPHY.

Lead shields are commonly used in X-ray imaging to protect radiosensitive organs and to minimise patient's radiation dose. However, they might also complicate or interfere with the examination, and even decrease the diagnostic value if they are positioned incorrectly. In this study, the radiation dose effect of waist half-apron lead shield was examined via Monte Carlo simulations of postero-anterior (PA) chest radiography examinations using a female anthropomorphic phantom. Relevant organs for dose determination were lungs, breasts, liver, kidneys and uterus. The organ dose reductions varied depending on shield position and organ but were negligible for properly positioned shields. The shield that had the largest effective dose reduction (9%) was partly positioned inside the field of view, which should not be done in practice. Dose reduction was practically 0% for properly positioned shields. Therefore, the use of lead shield in the pelvic region during chest PA examinations should be discontinued.

Volume matters: Breast induration is associated with irradiated breast volume in the Danish Breast Cancer Group phase III randomized Partial Breast Irradiation trial.

PURPOSE: The relation between breast induration grade 2-3 at 3 years after radiation therapy and irradiated breast volume was investigated for patients in the Danish Breast Cancer Group (DBCG) Partial Breast Irradiation (PBI) trial. METHODS Treatment plan data was obtained from the Danish radiotherapy plan database. Dosimetric parameters for breast and organs at risk were determined. Breast induration data was obtained from the DBCG database. The volume of the whole breast (CTVp_breast) treated to various dose levels was determined for treatment plans in both arms. Logistic regression was used to assess the frequency of induration on breast volume irradiated to ≥40 Gy. RESULTS PBI and WBI was given to 433 and 432 patients, respectively. Median and interquartile ranges (IQR) for CTVp_breast were 710 mL (467-963 mL; PBI) and 666 mL (443-1012 mL; WBI) (p = 0.98). Median and IQR for CTVp_breast treated to ≥40 Gy was 24.9% (18.6-32.6%; PBI) and 59.8% (53.6-68.5%; WBI). Grade 2-3 induration was observed in 5% (PBI) and 10% (WBI) of the patients. A dose-response relationship was established between irradiated breast volume and frequency of breast induration. From the model, 5% and 10% risks of breast induration were observed for ≥40 Gy delivered to CTVp_breast volumes of 177 mL (95%CI, 94-260 mL) and 426 mL (95%CI, 286-567 mL), respectively. CONCLUSION The frequency of breast induration increased significantly with increasing irradiated breast volume, strongly favouring small volumes and PBI. Thus, treated breast volume - not the breast size itself - is the risk factor for induration. This is the first report directly linking the 40 Gy irradiated breast volume to breast induration.

Partial Breast Irradiation Versus Whole Breast Irradiation for Early Breast Cancer Patients in a Randomized Phase III Trial: The Danish Breast Cancer Group Partial Breast Irradiation Trial.

PURPOSE: On the basis of low risk of local recurrence in elderly patients with breast cancer after conservative surgery followed by whole breast irradiation (WBI), the Danish Breast Cancer Group initiated the noninferiority external-beam partial breast irradiation (PBI) trial (ClinicalTrials.gov identifier: NCT00892814). We hypothesized that PBI was noninferior to WBI regarding breast induration. METHODS: Patients operated with breast conservation for relatively low-risk breast cancer were randomly assigned to WBI versus PBI, and all had 40 Gy/15 fractions. The primary end point was 3-year grade 2-3 breast induration. RESULTS: In total, 865 evaluable patients (434 WBI and 431 PBI) were enrolled between 2009 and 2016. Median follow-up was 5.0 years (morbidity) and 7.6 years (locoregional recurrence). The 3-year rate of induration was 9.7% for WBI and 5.1% for PBI (P = .014). Large breast size was significantly associated with induration with a 3-year incidence of 13% (WBI) and 6% (PBI) for large-breasted patients versus 6% (WBI) and 5% (PBI) for small-breasted patients. PBI showed no increased risk of dyspigmentation, telangiectasia, edema, or pain, and patient satisfaction was high. Letrozole and smoking did not increase the risk of radiation-associated morbidity. Sixteen patients had a locoregional recurrence (six WBI and 10 PBI; P = .28), 20 patients had a contralateral breast cancer, and eight patients had distant failure (five WBI and three PBI). A nonbreast second cancer was detected in 73 patients (8.4%), and there was no difference between groups. CONCLUSION: External-beam PBI for patients with low-risk breast cancer was noninferior to WBI in terms of breast induration. Large breast size was a risk factor for radiation-associated induration. Few recurrences were detected and unrelated to PBI.

Knowledge-based multi-institution plan prediction of whole breast irradiation with tangential fields.

PURPOSE: To quantify inter-institute variability of Knowledge-Based (KB) models for right breast cancer patients treated with tangential fields whole breast irradiation (WBI). MATERIALS AND METHODS: Ten institutions set KB models by using RapidPlan (Varian Inc.), following previously shared methodologies. Models were tested on 20 new patients from the same institutes, exporting DVH predictions of heart, ipsilateral lung, contralateral lung, and contralateral breast. Inter-institute variability was quantified by the inter-institute SDint of predicted DVHs/Dmean. Association between lung sparing vs PTV coverage strategy was also investigated. The transferability of models was evaluated by the overlap of each model's geometric Principal Component (PC1) when applied to the test patients of the other 9 institutes. RESULTS: The overall inter-institute variability of DVH/Dmean ipsilateral lung dose prediction, was less than 2% (20%-80% dose range) and 0.55 Gy respectively (1SD) for a 40 Gy in 15 fraction schedule; it was < 0.2 Gy for other OARs. Institute 6 showed the lowest mean dose prediction value and no overlap between PTV and ipsilateral lung. Once excluded, the predicted ipsilateral lung Dmean was correlated with median PTV D99% (R2 = 0.78). PC1 values were always within the range of applicability (90th percentile) for 7 models: for 2 models they were outside in 1/18 cases. For the model of institute 6, it failed in 7/18 cases. The impact of inter-institute variability of dose calculation was tested and found to be almost negligible. CONCLUSIONS: Results show limited inter-institute variability of plan prediction models translating in high inter-institute interchangeability, except for one of ten institutes. These results encourage future investigations in generating benchmarks for plan prediction incorporating inter-institute variability.