Effectiveness and toxicity of five-fraction prone accelerated partial breast irradiation.

PURPOSE: Our institution was an early adopter of 5-fraction accelerated partial breast irradiation (ABPI) to treat women with early-stage breast cancer. This study reports long-term oncologic and cosmetic outcomes. METHODS: We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Logistic regression models were used to identify factors associated with development of late toxicities, clinician, and patient-rated cosmesis. Kaplan-Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free survival (LR-RFS). RESULTS: 442 patients received APBI either daily (56%) or every other day (44%) in the prone position (92%). At a median follow-up of 48 months (range: 5.96-155 months), 12 (2.7%) patients developed a local recurrence (LR). Out of 258 patients with > 3-month toxicity data available, the most common late grade ≥ 2 adverse event was breast fibrosis (6.2%). On multivariate analysis, daily APBI treatment (vs every other day) did not correlate with an increased risk of any late grade ≥ 2 toxicity though it did correlate with a lower risk of any late grade ≥ 2 fibrosis. Overall, at a median follow-up of 80 months, the rates of good-excellent physician and patient-rated cosmesis were 95% and 85%, respectively, with no difference between patients treated on consecutive vs. every other day. On multivariate analysis, patients who did not receive any adjuvant therapy were at increased risk of developing a LR. Five-year OS, LRFS, and DFS were 97.2%, 97.7%, and 89.5%, respectively. CONCLUSIONS: Five-fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity, and excellent cosmesis at long-term follow-up.

Comparison of partial-breast irradiation and intraoperative radiation to whole-breast irradiation in early-stage breast cancer patients: a Kaplan-Meier-derived patient data meta-analysis.

PURPOSE: Partial breast irradiation (PBI) and intraoperative radiation (IORT) represent alternatives to whole breast irradiation (WBI) following breast conserving surgery. However, data is mixed regarding outcomes. We therefore performed a pooled analysis of Kaplan-Meier-derived patient data from randomized trials to evaluate the hypothesis that PBI and IORT have comparable long-term rates of ipsilateral breast tumor recurrence as WBI. METHODS: In February, 2023, PubMed, EMBASE and Cochrane Central were systematically searched for randomized phase 3 trials of early-stage breast cancer patients undergoing breast-conserving surgery with PBI or IORT as compared to WBI. Time-to-event outcomes of interest included ipsilateral breast tumor recurrence (IBTR), overall survival (OS) and distant disease-free survival (DDFS). Statistical analysis was performed with R Statistical Software. RESULTS: Eleven randomized trials comprising 15,460 patients were included; 7,675 (49.6%) patients were treated with standard or moderately hypofractionated WBI, 5,413 (35%) with PBI and 2,372 (15.3%) with IORT. Median follow-up was 9 years. PBI demonstrated comparable IBTR risk compared with WBI (HR 1.20; 95% CI 0.95-1.52; p = 0.12) with no differences in OS (HR 1.02; 95% CI 0.90-1.16; p = 0.70) or DDFS (HR 1.15; 95% CI 0.81-1.64; p = 0.43). In contrast, patients treated with IORT had a higher IBTR risk (HR 1.46; 95% CI 1.23-1.72; p < 0.01) compared with WBI with no difference in OS (HR 0.98; 95% CI 0.84-1.14; p = 0.81) or DDFS (HR 0.91; 95% CI 0.76-1.09; p = 0.31). CONCLUSION: For patients with early-stage breast cancer following breast-conserving surgery, PBI demonstrated no difference in IBTR as compared to WBI while IORT was inferior to WBI with respect to IBTR.

Intraoperative Radiation Therapy for Early-Stage Breast Cancer: Updated Outcomes from a Single-Institution Experience.

BACKGROUND: Increasingly, data have supported the use of partial-breast irradiation (PBI) for low-risk patients after breast-conserving surgery, with techniques allowing for completion of treatment in 1-3 weeks. Intraoperative radiation therapy (IORT) is an alternative to PBI. Our institution had used low-energy photon IORT (TARGIT) for more than a decade. The initial results demonstrated a 2% local recurrence rate with a short follow-up period of 2 years. This report presents updated outcomes during with 5-year follow-up. METHODS: A review of an institutional review board (IRB)-approved institutional registry was performed. The review identified 215 patients with early-stage breast cancer (stages 0-IIA) who received IORT. At the time of surgery, IORT was delivered with 20 Gy in a single fraction, with 5.1% (n = 11) of patients receiving additional whole-breast irradiation (WBI). RESULTS: The mean age at diagnosis was 71 years (range, 49-98 years), and the median follow-up was 5.7 years (interquartile range [IQR], 4.2-7.0 years). Of the 215 patients, 2.8% (n = 6) had ductal carcinoma in situ (DCIS), 90.7% (n = 195) had T1 disease, and 6.5% (n = 14) had T2 disease. Endocrine therapy was prescribed for 79% and chemotherapy for 1.4% of the patients. The 5-year rates were 5.3% for local recurrence, 6.4% for locoregional recurrence, and 2.7% for distant metastases. At 5 years, 93% of the patients were alive. CONCLUSIONS: The 5-year outcomes with TARGIT IORT demonstrated high rates of local recurrence, exceeding those seen with alternative modern approaches. The local recurrence outcomes with IORT are more consistent with studies omitting radiation following breast-conserving surgery, using endocrine therapy alone. Consistent with current guidelines and previous data, TARGIT IORT should not be used as monotherapy outside prospective clinical trials.

Major complications after intraoperative radiotherapy with low-energy x-rays in early breast cancer.

PURPOSE: To describe and analyze major local complications after intraoperative radiotherapy (IORT) with low-energy x­rays during breast-conserving surgery (BCS) in early breast cancer. METHODS: Ten women out of 408 who were treated with IORT between 2002 and 2017 and subsequently developed a severe local complication requiring surgical intervention were retrospectively identified and analyzed. Demographic, clinical, and surgical parameters as well as complication characteristics and treatment methods were evaluated. RESULTS: At initial presentation, eight patients (80%) showed redness, six (60%) seroma, six (60%) wound infection, six (60%) suture dehiscence, and four (40%) induration of the former surgical area. Hematoma and necrosis were observed in one case (10%) each. Time interval until appearance of the first symptoms ranged from directly postoperative until 15 years postoperatively (median 3.1 months). Initial treatment modalities comprised antibiotic therapy (n = 8/80%) and transcutaneous aspiration of seroma (n = 3/30%). In the majority of patients, smaller surgical interventions (excision of a necrotic area/fistula [n = 6/60%] or secondary suture [n = 5/50%]) were sufficient to overcome the complication, yet larger interventions such as complex flap surgery and mastectomy were necessary in one patient each. CONCLUSION: IORT is an efficient and safe treatment method as < 2.5% of all IORT patients experienced major local complications. However, it seems to pose the risk of causing severe local complications that may require lengthy and burdensome treatment. Thorough preoperative counseling, implementation of recommended intraoperative precautions, and high vigilance for first symptoms of complications during follow-up appointments are necessary measures.

Intraoperative radiotherapy (IORT) of early breast cancer with low-energy x-rays in breast-conserving surgery : Prospective identification of pre- and intraoperative factors influencing the feasibility of IORT.

PURPOSE: The aim of this study is to identify pre- and intraoperative factors indicating the feasibility of intraoperative radiotherapy (IORT) during breast-conserving surgery (BCS). MATERIALS AND METHODS: From January 2018 to December 2019, a total of 128 women undergoing BCS due to early breast cancer were included in this prospective observational study, independent of whether IORT was planned or not. Patient and tumor characteristics as well as surgical parameters that could potentially influence the feasibility of IORT were recorded for the entire collective. In addition, a preoperative senological assessment was performed and analyzed to assess the feasibility of IORT. Logistic regression was then used to identify relevant preoperative parameters and to generate a formula predicting the feasibility of IORT. RESULTS: Of the 128 included women undergoing BCS, 46 were preoperatively rated to be feasible, 20 to be questionably feasible for IORT. Ultimately, IORT was realized in 30 patients. The most frequent reasons for omission of IORT were insufficient tumor-to-skin distance and/or an excessively large tumor cavity. Small clinical tumor size and large tumor-to-skin distance according to preoperative ultrasound were significantly related to accomplishment of IORT. CONCLUSION: We observed that preoperative ultrasound-based tumor-skin distance is a significant factor in addition to already known parameters to predict feasibility of IORT. Based on our findings we developed a formula to optimize IORT planning which might serve as an additional tool to improve patient selection for IORT in early breast cancer.

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.

Prediction of pathologic complete response after single-dose MR-guided partial breast irradiation in low-risk breast cancer patients: the ABLATIVE-2 trial-a study protocol.

BACKGROUND: Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients. METHODS: The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy. DISCUSSION: This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6-8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients. TRIAL REGISTRATION: The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).

A Precise Approach for Radiotherapy of Breast Cancer.

Radiotherapy is an integral part of the multidisciplinary management of breast cancer (BC). There have been multiple recent advances in the delivery of radiotherapy, reviewed with a critical discussion of the evidence from trials investigating adjuvant ultra-hypofractionation and partial breast irradiation for early-stage BC, and the locoregional management of lymph nodes in locally advanced BC. Multiple precision medicine-based approaches have been developed as prognostic and/or predictive for BC patients and identifying biomarkers of radioresistance could help identify patients that may benefit from dose-escalated radiotherapy or radiosensitizers. Radiotherapy after breast reconstruction is an area of current controversy in the field, and we evaluated the decision-making considerations in this situation. The oligometastatic state is an emerging field for many cancer sites based on recent trials investigating ablative radiotherapy for oligometastatic BC. This chapter is an overview of radiotherapy for BC, with a focus on recent advances in early-stage, locally advanced, and oligometastatic disease.

On the feasibility of improved target coverage without compromising organs at risk using online adaptive stereotactic partial breast irradiation (A-SPBI).

PURPOSE: Describe an early-adopting institution's experience with online adaptive radiation for stereotactic partial breast irradiation. METHODS AND MATERIALS: Retrospective review of 22 women treated between May 2021 and March 2022 with adaptive stereotactic partial breast irradiation. A total of 106 of 110 fractions were evaluated for dosimetric changes in target coverage and organ-at-risk (OAR) dose. Patient set up with stereotactic wooden frame and adapted per fraction. Treatment and planning times were collected prospectively by radiation therapists. RESULTS: Scheduled PTV30 Gy was <95% in 72.1% and <90% in 38.5% of fractions, and both PTV and CTV coverage were improved significantly after adaption, and 83.7% of fractions were delivered as adapted per physician choice. There was no difference in OAR coverage. Average adaptive treatment planning took 15 min and average time-on-couch was 34.4 min. CONCLUSIONS: Adaptive stereotactic breast irradiation resulted in improved target coverage with equivalent dosing to OARs in an efficient and tolerated treatment time. Improved target coverage allowed for decreased PTV margins compared to prior trial protocols that may improve acute and late toxicities.

Intraoperative electron radiotherapy in early invasive ductal breast cancer: 6-year median follow-up results of a prospective monocentric registry.

BACKGROUND: Intraoperative electron radiotherapy (IOERT) can be used to treat early breast cancer during the conservative surgery thus enabling shorter overall treatment times and reduced irradiation of organs at risk. We report on our first 996 patients enrolled prospectively in a registry trial. METHODS: At Jules Bordet Institute, from February 2010 onwards, patients underwent partial IOERT of the breast. Women with unifocal invasive ductal carcinoma, aged 40 years or older, with a clinical tumour size ≤ 20 mm and tumour-free sentinel lymph node (on frozen section and immunohistochemical analysis). A 21 Gy dose was prescribed on the 90% isodose line in the tumour bed with the energy of 6 to 12 MeV (Mobetron®-IntraOp Medical). RESULTS: Thirty-seven ipsilateral tumour relapses occurred. Sixteen of those were in the same breast quadrant. Sixty patients died, and among those, 12 deaths were due to breast cancer. With 71.9 months of median follow-up, the 5-year Kaplan-Meier estimate of local recurrence was 2.7%. CONCLUSIONS: The rate of breast cancer local recurrence after IOERT is low and comparable to published results for IORT and APBI. IOERT is highly operator-dependent, and appropriate applicator sizing according to tumour size is critical. When used in a selected patient population, IOERT achieves a good balance between tumour control and late radiotherapy-mediated toxicity morbidity and mortality thanks to insignificant irradiation of organs at risk.

Hypofractionated proton therapy in breast cancer: where are we? A critical review of the literature.

PURPOSE: To critically review available literature on hypofractionated (≥ 3 Gy/fraction) proton therapy (PT) for breast cancer (BCa). METHODS: A systematic screening of the literature was performed in April 2021 in compliance with the preferred reporting items for systematic reviews and meta-analyses recommendations. All full-text publication written in English were considered eligible. Acute and late toxicities, oncological outcomes and dosimetric features were considered for the analysis. RESULTS: Twelve publications met the inclusion criteria; all studies but one focused on accelerated partial breast irradiation (APBI). Eleven works considered post-operative patients, one referred to ABPI as a curative-intent modality. The dosimetric profile of PT compared favorably with both photon-based 3D conformal and intensity-modulated techniques, while a more extended follow-up is warranted to fully assess both the long-term toxicities and the non-inferiority of oncological outcomes. CONCLUSION: Our work shows that results on PT for BCa are currently only available for APBI applications, with dosimetric analyses demonstrating a clear advantage over both 3D conformal and intensity modulated X-rays techniques, especially when ≥ 2 treatment fields were used. However, further evidence is needed to define whether such theoretical benefit translates into clinical improvements, especially in the long-term.

Estimation of secondary cancer projected risk after partial breast irradiation at the 1.5 T MR-linac.

PURPOSE: For patients treated with partial breast irradiation (PBI), potential long-term treatment-related toxicities are important. The 1.5 T magnetic resonance guided linear accelerator (MRL) offers excellent tumor bed visualization and a daily treatment plan adaption possibility, but MRL-specific electron stream and return effects may cause increased dose deposition at air-tissue interfaces. In this study, we aimed to investigate the projected risk of radiation-induced secondary malignancies (RISM) in patients treated with PBI at the 1.5 T MRL. METHODS: Projected excess absolute risk values (EARs) for the contralateral breast, lungs, thyroid and esophagus were estimated for 11 patients treated with PBI at the MRL and compared to 11 patients treated with PBI and 11 patients treated with whole breast irradiation (WBI) at the conventional linac (CTL). All patients received 40.05 Gy in 15 fractions. For patients treated at the CTL, additional dose due to daily cone beam computed tomography (CBCT) was simulated. The t­test with Bonferroni correction was used for comparison. RESULTS: The highest projected risk for a radiation-induced secondary cancer was found for the ipsilateral lung, without significant differences between the groups. A lower contralateral breast EAR was found for MRL-PBI (EAR = 0.89) compared to CTL-PBI (EAR = 1.41, p = 0.01), whereas a lower thyroid EAR for CTL-PBI (EAR = 0.17) compared to MRL-PBI (EAR = 0.33, p = 0.03) and CTL-WBI (EAR = 0.46, p = 0.002) was observed. Nevertheless, when adding the CBCT dose no difference between thyroid EAR for CTL-PBI compared to MRL-PBI was detected. CONCLUSION: Better breast tissue visualization and the possibility for daily plan adaption make PBI at the 1.5 T MRL particularly attractive. Our simulations suggest that this treatment can be performed without additional projected risk of RISM.

The Italian Association for Radiotherapy and Clinical Oncology (AIRO) position statements for postoperative breast cancer radiation therapy volume, dose, and fractionation.

Recent advances in non-metastatic breast cancer radiation therapy significantly reshaped our views on modern dose and fractionation schedules. Especially the advent of hypofractionation and partial breast irradiation defined a new concept of treatment optimization, that should strongly include both patient and tumour characteristics in the physician's decision-making process. Unfortunately, hypofractionation for breast cancer radiation therapy needed long time to enter the routine practice during the last decades despite the level-1 evidence published over time. Hereby we present the Italian Association for Radiotherapy and Clinical Oncology (AIRO) Breast Cancer Group position statements for postoperative breast cancer radiation therapy volume, dose, and fractionation to harmonically boost routine clinical practice implementation following evidence-based data.

Increased Risk for Ipsilateral Breast Tumor Recurrence in Invasive Lobular Carcinoma after Accelerated Partial Breast Irradiation Brachytherapy.

BACKGROUND: The suitability criteria for accelerated partial breast irradiation (APBI) from the American Brachytherapy Society (ABS), American Society for Radiation Oncology (ASTRO), and The Groupe Européende Curiethérapie European SocieTy for Radiotherapy & Oncology (GEC-ESTRO) have significant differences. MATERIALS AND METHODS: This is a single institution retrospective review of 946 consecutive patients with invasive breast cancer who underwent lumpectomy and APBI intracavitary brachytherapy from 2003 to 2018. Overall survival (OS), breast cancer-specific survival (BCSS), relapse-free survival (RFS), and ipsilateral breast tumor recurrence (IBTR) were estimated with Kaplan-Meier method. RESULTS: Median follow-up time was 60.2 months. Median age was 68 years (46-94 years). The majority of patients had estrogen receptor (ER)-positive disease (94%). There were 821 (87%) cases of invasive ductal carcinoma and 68 cases (7%) of invasive lobular carcinoma (ILC). The 5-year OS, BCSS, RFS, and IBTR were 93%, 99%, 90%, and 1.5%, respectively. Upon univariate analysis, ILC (hazard ratio [HR], 4.6; p = .008) and lack of nodal evaluation (HR, 6.9; p = .01) were risk factors for IBTR. The 10-year IBTR was 2.5% for IDC and 14% for ILC. While the ABS and ASTRO criteria could not predict IBTR, the GEC-ESTRO intermediate risk group was associated with inferior IBTR (p = .04) when compared to both low risk and high risk groups. None of the suitability criteria was able to predict RFS. CONCLUSION: These results show that APBI is an effective treatment for patients with invasive breast cancer. Expansion of the current eligibility criteria should be considered, although prospective validation is needed. Caution is required when considering APBI for patients with ILC. IMPLICATIONS FOR PRACTICE: In a large retrospective review of 946 patients with early breast cancer treated with partial mastectomy and accelerated partial breast irradiation (APBI) intracavitary brachytherapy, this study demonstrates durable local control. Patients deemed unsuitable or high risk by the American Brachytherapy Society, American Society for Radiation Oncology, and European Society for Radiotherapy and Oncology guidelines were not at increased risk for ipsilateral breast tumor recurrence (IBTR), suggesting that expansion of the current criteria should be considered. Importantly, however, these results demonstrate that caution should be taken when considering APBI for patients with invasive lobular carcinoma, as these patients had relatively high risk for IBTR (10-year IBTR, 14%).

Can we rely on surgical clips placed during oncoplastic breast surgery to accurately delineate the tumor bed for targeted breast radiotherapy?

PURPOSE: Oncoplastic breast surgery (OBS) is gaining popularity among surgeons for breast-conserving surgery treatments. OBS relies on complex relocation and deformation of breast tissue involving the tumor bed (TB). In this study, we investigate the validity of using surgical clips with OBS for accurate TB delineation in adjuvant, targeted breast radiotherapy. METHODS: Different OBS techniques were simulated on realistic breast phantoms. Surgical clips were used to demarcate the TB. Following tumor resection and closure, the true TB (TBTrue) was extracted. Each phantom was CT imaged at several phases of surgery in order to record pre- and post-OBS closure surgical clip displacements. Two senior radiation oncologists (ROs) were asked to delineate TBs on CTs by relying on surgical clips placed as per standard protocol, and by referring to operative notes. Their original contours, as well as those expanded using 5-15 mm margins, were compared with the accurate TBTrue using the dice similarity coefficient (DSC), Hausdorff Distance (HD), and over- and under-contoured volumes. Inter- and intra-RO contour agreements were also evaluated. RESULTS: Post-OBS surgical clips were significantly displaced outside the original breast quadrant. Inter- and Intra-RO TB contours were consistent, yet systematically differed from TBTrue (DSC values range = 0.38 to 0.69, and maximum HD range = 17.8 mm to 38.0 mm). Using expansion margins did not improve contour congruence and caused significant over-contoured volumes. CONCLUSION: Following OBS, surgical clips alone are not reliable radiographic surrogates of TB locations and accurate TB delineation is challenging. For complex OBS cases, indication of any type of partial breast irradiation is very questionable.

Health-related quality of life of early-stage breast cancer patients after different radiotherapy regimens.

PURPOSE: To evaluate and compare health-related quality of life (HRQL) of women with early-stage breast cancer (BC) treated with different radiotherapy (RT) regimens. METHODS: Data were collected from five prospective cohorts of BC patients treated with breast-conserving surgery and different RT regimens: intraoperative RT (IORT, 1 × 23.3 Gy; n = 267), external beam accelerated partial breast irradiation (EB-APBI, 10 × 3.85 Gy; n = 206), hypofractionated whole breast irradiation(hypo-WBI, 16 × 2.67 Gy; n = 375), hypo-WBI + boost(hypo-WBI-B, 21-26 × 2.67 Gy; n = 189), and simultaneous WBI + boost(WBI-B, 28 × 2.3 Gy; n = 475). Women ≥ 60 years with invasive/in situ carcinoma ≤ 30 mm, cN0 and pN0-1a were included. Validated EORTC QLQ-C30/BR23 questionnaires were used to asses HRQL. Multivariable linear regression models adjusted for confounding (age, comorbidity, pT, locoregional treatment, systemic therapy) were used to compare the impact of the RT regimens on HRQL at 12 and 24 months. Differences in HRQL over time (3-24 months) were evaluated using linear mixed models. RESULTS: There were no significant differences in HRQL at 12 months between groups except for breast symptoms which were better after IORT and EB-APBI compared to hypo-WBI at 12 months (p < 0.001). Over time, breast symptoms, fatigue, global health status and role functioning were significantly better after IORT and EB-APBI than hypo-WBI. At 24 months, HRQL was comparable in all groups. CONCLUSION: In women with early-stage breast cancer, the radiotherapy regimen did not substantially influence long-term HRQL with the exception of breast symptoms. Breast symptoms are more common after WBI than after IORT or EB-APBI and improve slowly until no significant difference remains at 2 years posttreatment.

Progress and controversies: radiation therapy for invasive breast cancer.

Radiation therapy is a critical component of the multidisciplinary management of invasive breast cancer. In appropriately selected patients, radiation not only improves local control, sparing patients the morbidity and distress of local recurrence, but it also improves survival by preventing seeding and reseeding of distant metastases from persistent reservoirs of locoregional disease. In recent years, considerable progress has been made toward improving our ability to select patients most likely to benefit from radiotherapy and to administer treatment in ways that maximize clinical benefit while minimizing toxicity and burden. This article reviews the role of radiation therapy in invasive breast cancer management, both after breast-conserving surgery and after mastectomy. It focuses particularly on emerging evidence that helps to define the clinical situations in which radiotherapy is indicated, the appropriate targets of treatment, and optimal approaches for minimizing both the toxicity and the burden of treatment, all in the context of the evolving surgical and systemic management of this common disease. It includes a discussion of new approaches in breast cancer radiotherapy, including hypofractionation and intensity modulation, as well as a discussion of promising avenues for future research.

Secondary angiosarcoma following catheter-based brachytherapy.

Secondary angiosarcoma of the breast following catheter-based brachytherapy after lumpectomy is rare. We describe a case of a patient with breast cancer treated with partial mastectomy and sentinel node biopsy followed by accelerated partial breast irradiation (APBI), who developed skin changes 6 years after completion of therapy. Punch biopsy confirmed the diagnosis of secondary angiosarcoma. This case is even more unique in that the location of the skin changes was remote to the lumpectomy site. There is a critical need to recognize secondary angiosarcoma presentation after APBI and determine the rate of occurrence compared with traditional external beam irradiation.

Dosimetric characteristics of accelerated partial breast irradiation by interstitial multicatheter brachytherapy with intraoperative free-hand implantation in the treatment of early breast cancer.

INTRODUCTION: The aim of this study is to evaluate the characteristics of the dosimetry and the skin dose of interstitial brachytherapy by the use of the free-hand implantation technique toward the treatment of early breast cancer. MATERIALS & METHODS: Seventeen patients diagnosed with early breast cancer were selected for the study. The implantation of the catheters for postoperative interstitial brachytherapy was performed using the free-hand technique. The total tumor dose to the tumor cavity plus 2 cm margin was 3400 cGy, twice daily for 10 fractions in 5 days. The dosage to the target and the organ at risk (OAR) were recorded for analysis. The skin dose of the patient and the phantom were measured with Gafchromic film (EBT3) and the results were compared with the skin dose calculated by the brachytherapy treatment planning system. RESULTS: The median conformal index is 94% (range 89%-99%), and the median homogeneity index is 71%. The median skin dose measured from the skin of the patients was 20.1% lower than the skin dose calculated from the treatment planning system and consistent with the phantom surface measurement experiment. There were no grade 3 or above acute toxicity recorded. CONCLUSIONS: Interstitial brachytherapy by the use of the free-hand implantation technique for early breast cancer is feasible and avoids the need for a second surgical intervention. The calculated skin dose was overestimated by at least 20%. The results of this study may help in building a modification model for the prediction of skin toxicity in any future study.

Individually selected teletherapy technique for accelerated partial breast irradiation.

BACKGROUND: The aim of the study was to individualize accelerated partial breast irradiation based on optimal dose distribution, protect risk organ and predict most advantageous technique. MATERIALS AND METHODS: 138 breast cancer patients receiving postoperative APBI were enrolled. APBI plans were generated using 3D-conformal (3D-CRT), sliding window intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT). In the case of superficial tumours, additional plans were developed by adding electron beam. To planning target volume (PTV) 37.5 Gy/10 fractions, 1 fraction/day was prescribed. A novel plan quality index (PQI) served as the basis for comparisons. RESULTS: IMRT was the most advantageous technique regarding homogeneity. VMAT provided best conformity, 3D-CR T - the lowest lung and heart exposure. PQI was the best in 45 (32.61%) VMAT, 13 (9.42%) IMRT, 9 (6.52%) 3D-CRT plans. In 71 cases (51.45%) no difference was detected. In patients with large PTV, 3D-CRT was the most favourable. Additional electron beam improved PQI of 3D-CRT plans but had no meaningful effect on IMRT or VMAT. IMRT was superior to VMAT if the tumour was superficial (p < 0.001), situated in the medial (p = 0.032) or upper quadrant (p = 0.046). CONCLUSIONS: In half of all cases, individually selected teletherapy techniques provide superior results over others; relevance of a certain technique may be predicted by volume and PTV localization.