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

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

Hsa-miR-375 is a predictor of local control in early stage breast cancer

Background: A long-term analysis by the Early Breast Cancer Trialist Group (EBCTG) revealed a strong correlation between local control and cancer-specific mortality. MicroRNAs (miRs), short (20-25 nucleotides) non-coding RNAs, have been described as prognosticators and predictors for breast cancer in recent years. The aim of the current study was to identify miRs that can predict local control after breast conserving therapy (BCT) in early stage breast cancer. Results: Clinical data of 46 early stage breast cancer patients with local relapse after BCT were selected from the institutional database. These patients were matched to 101 control patients showing identical clinical features but without local relapse. The study was conducted in two steps. (1) In the pilot study, 32 patients (16 relapses versus 16 controls) were screened for the most de-regulated microRNAs (= candidate microRNAs) in a panel of 1250 miRs by microarray technology. Eight miRs were found to be significantly de-regulated. (2) In the validation study, the candidate microRNAs were analyzed in an independent cohort of 115 patients (30 relapses versus 85 controls) with reverse transcription quantitative polymerase chain reaction (RT-qPCR). From these eight candidates, hsa-miR-375 could be validated. Its median fold change was 2.28 (Mann-Whitney U test, corrected p value = 0.008). In the log-rank analysis, high expression levels of hsa-miR-375 correlated with a significantly higher risk of local relapse (p = 0.003). In a multivariate analysis (forward stepwise regression) including established predictors and prognosticators, hsa-miR-375 was the only variable that was able to distinguish the statistical significance between relapse and control groups (raw p value = 0.000195 HR = 0.76, 95 % CI 0.66-0.88;corrected p value = 0.005). Conclusions: Hsa-miR-375 predicts local control in patient with early stage breast cancer, especially in estrogen receptor alpha (ER-alpha)-positive patients. It can therefore serve as an additional molecular marker for treatment choice independently from known predictors and prognosticators. Validation in larger prospective studies is warranted

Normal tissue complication models for clinically relevant acute esophagitis (>= grade 2) in patients treated with dose differentiated accelerated radiotherapy (DART-bid)

Background: One of the primary dose-limiting toxicities during thoracic irradiation is acute esophagitis (AE). The aim of this study is to investigate dosimetric and clinical predictors for AE grade >= 2 in patients treated with accelerated radiotherapy for locally advanced non-small cell lung cancer (NSCLC). Patients and methods: 66 NSCLC patients were included in the present analysis: 4 stage II, 44 stage IIIA and 18 stage IIIB. All patients received induction chemotherapy followed by dose differentiated accelerated radiotherapy (DART-bid). Depending on size (mean of three perpendicular diameters) tumors were binned in four dose groups: 6 cm 90 Gy. Patients were treated in 3D target splitting technique. In order to estimate the normal tissue complication probability (NTCP),two Lyman models and the cutoff-logistic regression model were fitted to the data with AE >= grade 2 as statistical endpoint. Inter-model comparison was performed with the corrected Akaike information criterion (AIC(c)),which calculates the model's quality of fit (likelihood value) in relation to its complexity (i.e. number of variables in the model) corrected by the number of patients in the dataset. Toxicity was documented prospectively according to RTOG. Results: The median follow up was 686 days (range 84-2921 days), 23/66 patients (35 %) experienced AE >= grade 2. The actuarial local control rates were 72.6 % and 59.4 % at 2 and 3 years, regional control was 91 % at both time points. The Lyman-MED model (D50 = 32.8 Gy, m = 0.48) and the cutoff dose model (D-c = 38 Gy) provide the most efficient fit to the current dataset. On multivariate analysis V38 (volume of the esophagus that receives 38 Gy or above, 95 %-CI 28.2-57.3) was the most significant predictor of AE >= grade 2 (HR = 1.05, CI 1.01-1.09, p = 0.007). Conclusion: Following high-dose accelerated radiotherapy the rate of AE >= grade 2 is slightly lower than reported for concomitant radio-chemotherapy with the additional benefit of markedly increased loco-regional tumor control. In the current patient cohort the most significant predictor of AE was found to be V38. A second clinically useful parameter in treatment planning may be MED (mean esophageal dose)

Boost IORT in Breast Cancer: Body of Evidence

The term IORT (intraoperative radiotherapy) is currently used for various techniques that show decisive differences in dose delivery. The largest evidence for boost IORT preceding whole breast irradiation (WBI) originates from intraoperative electron treatments with single doses around 10 Gy, providing outstandingly low local recurrence rates in any risk constellation also at long term analyses. Compared to other boost methods, an intraoperative treatment has evident advantages as follows. Precision. Direct visualisation of the tumour bed during surgery guarantees an accurate dose delivery. This fact has additionally gained importance in times of primary reconstruction techniques after lumpectomy to optimise cosmetic outcome. IORT is performed before breast tissue is mobilised for plastic purposes. Cosmesis. As a consequence of direct tissue exposure without distension by hematoma/seroma, IORT allows for small treatment volumes and complete skin sparing, both having a positive effect on late tissue tolerance and, hence, cosmetic appearance. Patient Comfort. Boost IORT marginally prolongs the surgical procedure, while significantly shortening postoperative radiotherapy. Its combination with a 3-week hypofractionated external beam radiotherapy to the whole breast (WBI) is presently tested in the HIOB trial (hypofractionated WBI preceded by IORT electron boost), a prospective multicenter trial of the International Society of Intraoperative Radiotherapy (ISIORT)

Oligometastasis in breast cancer-current status and treatment options from a radiation oncology perspective

Evidence from a few small randomized trials and retrospective cohorts mostly including various tumor entities indicates a prolongation of disease free survival (DFS) and overall survival (OS) from local ablative therapies in oligometastatic disease (OMD). However, it is still unclear which patients benefit most from this approach. We give an overview of the several aspects of stereotactic body radiotherapy (SBRT) in extracranial OMD in breast cancer from a radiation oncology perspective. A PubMed search referring to this was conducted. An attempt was made to relate the therapeutic efficacy of SBRT to various prognostic factors. Data from approximately 500 breast cancer patients treated with SBRT for OMD in mostly in small cohort studies have been published, consistently indicating high local tumor control rates and favorable progression-free (PFS) and overall survival (OS). Predictors for a good prognosis after SBRT are favorable biological subtype (hormone receptor positive, HER2 negative), solitary metastasis, bone-only metastasis, and long metastasis-free interval. However, definitive proof that SBRT in OMD breast cancer prolongs DFS or OS is lacking, since, with the exception of one small randomized trial (n = 22 in the SBRT arm), none of the cohort studies had an adequate control group. Further studies are needed to prove the benefit of SBRT in OMD breast cancer and to define adequate selection criteria. Currently, the use of local ablative SBRT should always be discussed in a multidisciplinary tumor board

Intraoperative radiotherapy (IORT) as boost in breast cancer

The term IORT (intraoperative radiotherapy) is currently used for various techniques that show huge differences in dose delivery and coverage of the tissue at risk. The largest evidence for boost IORT preceding whole breast irradiation (WBI) originates from intraoperative electron treatments (IOERT) with single doses around 10 Gy. At median follow-up periods at 6 years, outstandingly low local recurrence rates of less than 1% are observed. Higher local relapse rates were described for G3 tumors and triple negative breast cancers as well as for IORT following primary systemic treatment for locally advanced tumors. Even there, long term (>5y) local tumor control rates mostly beyond 95% were maintained. Compared to other boost methods, an intraoperative treatment has evident advantages in terms of precision (by avoiding a “spatial and/or temporal miss”), cosmetic outcome and patient comfort. Direct visualisation of a tumor bed during surgery guarantees for an accurate dose delivery, which has additionally gained importance in times of primary reconstruction techniques after lumpectomy, since IORT is performed before breast tissue including parts of the tumor bed is mobilized for plastic purposes. As a consequence of direct tissue exposure without distension by hematoma/seroma, IORT allows for small treatment volumes and complete skin sparing, both having a positive effect on late tissue tolerance and, hence, cosmetic appearance. Boost IORT marginally prolongs the surgical procedure, while significantly shortening postoperative radiotherapy. Its combination with external beam radiotherapy to the whole breast (WBI) is currently tested in two multicentric prospective trials: as kV-IORT in the multicentric TARGIT-B (oost) study, and as IOERT in the HIOB trial (3 weeks hypofractionated WBI preceded by IORT electron boost)

Oligometastasis in breast cancer—current status and treatment options from a radiation oncology perspective

Evidence from a few small randomized trials and retrospective cohorts mostly including various tumor entities indicates a prolongation of disease free survival (DFS) and overall survival (OS) from local ablative therapies in oligometastatic disease (OMD). However, it is still unclear which patients benefit most from this approach. We give an overview of the several aspects of stereotactic body radiotherapy (SBRT) in extracranial OMD in breast cancer from a radiation oncology perspective. A PubMed search referring to this was conducted. An attempt was made to relate the therapeutic efficacy of SBRT to various prognostic factors. Data from approximately 500 breast cancer patients treated with SBRT for OMD in mostly in small cohort studies have been published, consistently indicating high local tumor control rates and favorable progression-free (PFS) and overall survival (OS). Predictors for a good prognosis after SBRT are favorable biological subtype (hormone receptor positive, HER2 negative), solitary metastasis, bone-only metastasis, and long metastasis-free interval. However, definitive proof that SBRT in OMD breast cancer prolongs DFS or OS is lacking, since, with the exception of one small randomized trial ( n  = 22 in the SBRT arm), none of the cohort studies had an adequate control group. Further studies are needed to prove the benefit of SBRT in OMD breast cancer and to define adequate selection criteria. Currently, the use of local ablative SBRT should always be discussed in a multidisciplinary tumor board.Open Access funding enabled and organized by Projekt DEAL.HELIOS Universitätsklinikum Wuppertal (8989

DEGRO guideline for personalized radiotherapy of brain metastases and leptomeningeal carcinomatosis in patients with breast cancer

Purpose The aim of this review was to evaluate the existing evidence for radiotherapy for brain metastases in breast cancer patients and provide recommendations for the use of radiotherapy for brain metastases and leptomeningeal carcinomatosis. Materials and methods For the current review, a PubMed search was conducted including articles from 01/1985 to 05/2023. The search was performed using the following terms: (brain metastases OR leptomeningeal carcinomatosis) AND (breast cancer OR breast) AND (radiotherapy OR ablative radiotherapy OR radiosurgery OR stereotactic OR radiation). Conclusion and recommendations Despite the fact that the biological subtype of breast cancer influences both the occurrence and relapse patterns of breast cancer brain metastases (BCBM), for most scenarios, no specific recommendations regarding radiotherapy can be made based on the existing evidence. For a limited number of BCBM (1–4), stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SRT) is generally recommended irrespective of molecular subtype and concurrent/planned systemic therapy. In patients with 5–10 oligo-brain metastases, these techniques can also be conditionally recommended. For multiple, especially symptomatic BCBM, whole-brain radiotherapy (WBRT), if possible with hippocampal sparing, is recommended. In cases of multiple asymptomatic BCBM (≥ 5), if SRS/SRT is not feasible or in disseminated brain metastases (> 10), postponing WBRT with early reassessment and reevaluation of local treatment options (8–12 weeks) may be discussed if a HER2/Neu-targeting systemic therapy with significant response rates in the central nervous system (CNS) is being used. In symptomatic leptomeningeal carcinomatosis, local radiotherapy (WBRT or local spinal irradiation) should be performed in addition to systemic therapy. In patients with disseminated leptomeningeal carcinomatosis in good clinical condition and with only limited or stable extra-CNS disease, craniospinal irradiation (CSI) may be considered. Data regarding the toxicity of combining systemic therapies with cranial and spinal radiotherapy are sparse. Therefore, no clear recommendations can be given, and each case should be discussed individually in an interdisciplinary setting.Open Access funding enabled and organized by Projekt DEAL.Technische Universität München (1025