Search Results (59)

Over the past two decades, interest in prone-position whole breast irradiation (WBI) as an effective and practical alternative to supine treatment has been growing a lot. Although solid scientific data has provided evidence of substantial dosimetric benefit with decreased toxicity, there is still conflict in the radiotherapy community over whether to adopt prone-position WBI as a valid alternative to supine radiotherapy (RT) in routine clinical practice. A large number of prone trials have been conducted to assess and address concerns related to prone treatment in large and pendulous breasts and in left and right breast cancer (BC), nodal irradiation, and its reproducibility with deep inspiration breath hold (DIBH) delivery with photons or protons. Appropriate atlases have been defined to improve prone nodal irradiation. Additionally, more comfortable customized immobilization couches have been constructed to permit IMRT beams and VMAT arrangements with modern LINACs. Although our search in literature databases shows a growing body of evidence from the past two decades on this issue, prone WBI is still underused. Given the paradox of the advances and benefits of this positioning and the lack of drive in the radiotherapy community towards its clinical implementation, the purpose of this comprehensive review is to evaluate the true advantages of this position in real life and contextualize it in scenarios like large breasts, left-sided breast cancer, and nodal irradiation to encourage its implementation in clinical practice. Full article

Background/Objectives: Patients with a diagnosis of ductal carcinoma in situ (DCIS) were poorly represented in the four trials that established the efficacy of partial relative to whole-breast irradiation. In contrast to invasive cancers, patients with DCIS are equally likely to have a subsequent ipsilateral invasive event in a different site of the breast from their initial DCIS lesion as they are at the same site. We aim to compare the efficacy of a type of partial-breast irradiation, brachytherapy, to external-beam radiation in the reduction of subsequent invasive cancers. Methods: Women diagnosed with a first breast cancer of unilateral DCIS treated with breast-conserving surgery without endocrine therapy were identified in SEER. Matching was performed 1:2 from patients receiving brachytherapy to patients receiving external-beam radiation or no radiation. External-beam radiation was assumed to be whole-breast radiation for the majority of patients in this cohort diagnosed from 2007 to 2011. Competing risks methods were used to estimate the cumulative incidence of invasive breast events at 10 years and subdistribution hazard ratios (sHRs) in adjusted models with time-varying treatment coefficients were calculated. Results: Among the 1392 matched patients who received brachytherapy or no radiation, the 10-year cumulative incidence of ipsilateral invasive cancer was 5.5% without radiation and 5.7% with brachytherapy (p = 0.92). Brachytherapy was associated with reduced risk of ipsilateral invasive events in the first 3 years (sHR = 0.19, p = 0.03) and non-significantly increased risk after 3 years (sHR = 1.66, p = 0.07). Among the 1392 matched patients who received brachytherapy or external-beam radiation, the 10-year cumulative incidence of ipsilateral invasive cancer was 5.7% with brachytherapy and 3.1% with external-beam radiation. In multivariate regression, brachytherapy was associated with unchanged risk in the first 3 years but increased risk after 3 years (sHR = 2.20, p = 0.009). Conclusions: Our results suggest that brachytherapy may be associated with a higher invasive recurrence risk for patients with DCIS treated without endocrine therapy, as it did not prevent more invasive ipsilateral events than no radiation, and provided reduced risk reduction in the ipsilateral breast relative to external-beam radiation. Further work is needed to identify if this is specific to brachytherapy or applies to all forms of partial-breast irradiation. Full article

To explore a more personalized approach to radiation therapy for adjuvant whole-breast irradiation in triple-negative breast cancer (TNBC), we analyzed the cell lines BT549 and MDA-MB-231 as in vitro models for radiobiological characterization. The local disease-free survival (LSR) values were determined for both cell lines’ median, maximum, and minimum α and β parameters to achieve an LSR probability of close to 100% in a five-fraction schedule. Based on these findings, fifteen treatment plans were created for BC to simulate the proposed dose schedule. For the MDA-MB-231 cell line, the α/β ratios were 3.79 Gy (minimum), 15 Gy (maximum), and 7 Gy (median). For the BT-549 cell line, the α/β ratios were 5.95 Gy (minimum), 22.93 Gy (maximum), and 16.51 Gy (median). To achieve an LSR probability of close to 100%, the required doses per fraction were 5.2 Gy, 5.3 Gy, and 7.3 Gy for MDA-MB-231 and 8 Gy, 9.1 Gy, and 9.9 Gy for BT-549. We selected the highest dose per fraction, 9.9 Gy × 5, to simulate the worst-case scenario. To achieve 100% cell death effectiveness in TNBC, it is likely that higher radiation doses are required—doses that are not feasible within the setting of adjuvant whole-breast irradiation. Our model, which relies on the intrinsic biological features of the tumor, paves the way to reach more tailored RT plans and to improve the classic LQ model. Full article

Advances in breast cancer treatment have shifted the focus from maximizing local control to balancing oncologic efficacy with treatment de-escalation and toxicity reduction. Whole-breast irradiation (WBI) following breast-conserving surgery remains the standard of care, but with up to 90% of recurrences occurring near the tumor bed, partial breast irradiation (PBI) has emerged as a viable alternative. Large randomized controlled trials (such as IMPORT LOW, Florence, and GEC-ESTRO) have demonstrated comparable ipsilateral breast tumor recurrence (IBTR) rates between PBI and WBI, reinforcing its oncologic safety in well-selected patients. However, challenges remain in optimizing fractionation schedules, refining patient selection, and minimizing late toxicity. Recent innovations, including MRI-guided radiotherapy (MRgRT) and neoadjuvant PBI, offer improved tumor targeting, real-time plan adaptation, and enhanced normal tissue sparing. These advancements hold promise for further reducing radiation-related morbidity and improving cosmetic outcomes. As PBI progresses, integrating novel imaging modalities and hypofractionated regimens will be crucial to refining protocols. This review synthesizes the latest evidence on PBI techniques, clinical outcomes, and emerging technologies to guide future research and clinical decision-making in precision breast radiotherapy. Full article

(1) Background: The management of ipsilateral breast cancer recurrence depends on the extent of the tumor, and staging results, and mastectomy is currently the standard of care for previously irradiated patients. Studies are increasingly investigating suitable candidates for the repeated use of breast-conserving approaches as an alternative to mastectomy. But this includes the crucial necessity for curative reirradiation (Re-RT). The therapeutic challenge in reirradiation involves finding a balance between tumor control and the risk of severe toxicity from cumulative radiation doses in previously irradiated organs. Re-RT options include the use of brachytherapy, intraoperative radiotherapy, or external beam RT with photons or electrons. The application of particle therapy using proton beam therapy represents an innovative radiotherapeutic technique for breast cancer patients that might offer advantageous physical properties, a superior dose reduction to adjacent organs-at-risk, and effective target volume coverage with lower integral doses to the patient’s whole body. In addition, this technique could potentially offer higher radiobiological effects and tumor responses. (2) Methods: The BREAST trial (NCT06954623) will be conducted as a prospective, single-arm, phase II study in 20 patients with histologically proven invasive breast cancer recurrences after repeat breast-conserving surgery and with an indication for local reirradiation. The patients will receive partial-breast re-RT with proton beam therapy in 15 once-daily fractions up to a total dose of 40.05 Gy(RBE), delivered with active raster scanning. The required time interval will be 1 year after previous RT to the ipsilateral breast. (3) Results: The following results will be reported: The primary endpoint is defined as the cumulative overall occurrence of (sub)acute skin toxicity of grade ≥ 3 within 6 months after the start of re-RT. Secondary outcome includes an analysis of the local, regional, and distant control, progression-free and overall survival, quality of life, and cosmesis. The explorative and translational objectives of this study include planning comparisons to other RT techniques and irradiation types, dosimetric evaluations, analyses of radiological imaging features, and translational assessments of cardiac toxicity biomarkers and tumor markers. (4) Conclusions: Overall, the aim of this study is to evaluate the potential of proton beam therapy for partial breast reirradiation and to establish the underlying data for a randomized trial. Full article

Background: Prone breast radiotherapy has been shown to optimally spare the dose to the heart and lungs; we report on the heart and left anterior descending coronary artery (LAD) dosimetry and their implications for current care. Aims: (I) To measure the mean heart dose (MHD) and LAD mean and maximum doses (Dmean and Dmax) in patients with left-side breast cancer who have undergone hypo-fractionated whole breast radiotherapy (WBRT) with a concomitant boost to the post-operative cavity (40.50 Gy to the breast and 48 Gy to the cavity in 15 fractions) in the prone position; (II) to compare the dosimetry results to those reported in the literature for other techniques. Materials and Methods: In a consecutive series of 524 irradiated left-side breast cancer patients, heart and LAD dosimetry data were collected and correlated to breast volume and the volume of the radiation boost to the tumor cavity. A descriptive statistical analysis was performed to compare the same dosimetry data with those reported in the literature from supine techniques. To account for dosimetry differences in hypo-fractionation and conventional fractionated regimens (50–60 Gy in 25–30 fractions) reported in the literature, the cardiac doses were converted to the equivalent dose in 2 Gy fractions (EQD2). As previously reported, the prone setup protocol placed the medial edges of the tangential radiation fields at least 2.5 mm from the contoured LAD. Results: In all patients’ plans, the target coverage was successfully achieved. The mean values (±SD) were as follows: MHD = 0.69 Gy (±0.19) (EQD2 0.35 Gy ± 0.1); LAD Dmean = 2.20 Gy (±0.68) (EQD2 1.18 Gy ± 0.35); LAD Dmax = 4.44 Gy (±1.82) (EQD2 2.55 Gy ± 0.97). The values were consistently lower compared with those achieved by the multiple supine techniques reported in the literature. Spearman’s correlation analysis revealed a strong positive correlation between LAD and heart dosimetry variables. In contrast, no strong correlation was observed between the cardiac dose metrics and breast volume, boost volume, or their ratio index. A linear correlation was detected between LAD Dmean and LAD D2% (R² 0.64); LAD D2% and heart D2% (R² 0.60); LAD Dmax and heart D2% (R² 0.41). Conclusions: The prone position protocol minimizes heart and LAD exposure. This approach results in a dosimetry advantage when compared with more complex and expensive WBRT techniques in the supine position. Full article

In radiation tumor therapy, irradiation, on one hand, should cause cell death to the tumor. On the other hand, the surrounding non-tumor tissue should be maintained unaffected. Therefore, methods of local dose enhancements are highly interesting. Gold nanoparticles, which are preferentially uptaken by very-fast-proliferating tumor cells, may enhance damaging. However, the results in the literature obtained from cell culture and animal tissue experiments are very contradictory, i.e., only some experiments reveal increased cell killing but others do not. Thus, a better understanding of cellular mechanisms is required. Using the breast cancer cell model SkBr3, the effects of gold nanoparticles in combination with ionizing radiation on chromatin network organization were investigated by Single-Molecule Localization Microscopy (SMLM) and applications of mathematical topology calculations (e.g., Persistent Homology, Principal Component Analysis, etc.). The data reveal a dose and nanoparticle dependent re-organization of chromatin, although colony forming assays do not show a significant reduction of cell survival after the application of gold nanoparticles to the cells. In addition, the spatial organization of γH2AX clusters was elucidated, and characteristic changes were obtained depending on dose and gold nanoparticle application. The results indicate a complex response of ALU-related chromatin and heterochromatin organization correlating to ionizing radiation and gold nanoparticle incorporation. Such complex whole chromatin re-organization is usually associated with changes in genome function and supports the hypothesis that, with the application of gold nanoparticles, not only is DNA damage increasing but also the efficiency of DNA repair may be increased. The understanding of complex chromatin responses might help to improve the gold nanoparticle efficiency in radiation treatment. Full article

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. Full article

Background: We aimed to construct an expert knowledge-based Bayesian network (BN) model for assessing the overall disease burden (ODB) in (y)pN1 breast cancer patients and compare ODB across arms of ongoing trials. Methods: Utilizing institutional data and expert surveys, we developed a BN model for (y)pN1 breast cancer. Expert-derived probabilities and disability weights for radiotherapy-related benefit (e.g., 7-year disease-free survival [DFS]) and toxicities were integrated into the model. ODB was defined as the sum of disability weights multiplied by probabilities. In silico predictions were conducted for Alliance A011202, PORT-N1, RAPCHEM, and RT-CHARM trials, comparing ODB, 7-year DFS, and side effects. Results: In the Alliance A011202 trial, 7-year DFS was 80.1% in both arms. Axillary lymph node dissection led to higher clinical lymphedema and ODB compared to sentinel lymph node biopsy with full regional nodal irradiation (RNI). In the PORT-N1 trial, the control arm (whole-breast irradiation [WBI] with RNI or post-mastectomy radiotherapy [PMRT]) had an ODB of 0.254, while the experimental arm (WBI alone or no PMRT) had an ODB of 0.255. In the RAPCHEM trial, the radiotherapy field did not impact the 7-year DFS in ypN1 patients. However, there was a mild ODB increase with a larger irradiation field. In the RT-CHARM trial, we identified factors associated with the major complication rate, which ranged from 18.3% to 22.1%. Conclusions: The expert knowledge-based BN model predicted ongoing trial outcomes, validating reported results and assumptions. In addition, the model demonstrated the ODB in different arms, with an emphasis on quality of life. Full article

Background: The current standard of local treatment for patients with localized breast cancer (BC) includes whole breast irradiation (WBI) after breast-conserving surgery (BCS). Ultrahypofractionated WBI schemes (1-week treatment) were shown not to be inferior to the standard WBI. Tumor bed boost using photon intraoperative radiotherapy (IORT) is safe and feasible in combination with standard WBI. The aim of the present study is to assess, for the first time, the feasibility and safety of combining photon IORT with ultrahypofractionated WBI. Methods: Patients diagnosed with low-risk early BC candidates for BCS were included in this prospective study. IORT was administered at a dose of 20 Gy to the surface’s applicator, and WBI was administered 3–5 weeks after surgery at a total dose of 26 Gy in five consecutive days. Results: From July 2020 to December 2022, seventy-two patients diagnosed with low-risk early BC and treated in our institution were included in this prospective study. All patients completed the proposed treatment, and no severe acute or late grade 3 toxicity was observed 3 and 12 months after WBI, respectively. Conclusions: Our results confirm for the first time that the combination of ultrafractionation WBI and photon-IORT after BCS is a feasible and safe option in patients with early BC. Full article

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. Full article

Purpose: Hydrofilm, a polyurethane-based barrier film, can be used to prevent acute radiation dermatitis (RD) in adjuvant whole-breast irradiation (WBI) for breast cancer. This cost-effective prophylactic measure is currently being recommended to a growing number of patients, yet long-term safety data and its impact on late radiation-induced skin toxicity such as pigmentation changes and fibrosis have not been investigated. Methods: We objectively evaluated patients who were previously enrolled in either of two intrapatient-randomised (lateral versus medial breast halve) controlled trials on the use of Hydrofilm for RD prevention (DRKS00029665; registered on 19 July 2022). Results: Sixty-two patients (47.7% of the initial combined sample size) provided consent for this post-hoc examination, with a median follow-up time (range) of 58 (37–73) months. Following WBI, there was a significant increase in yellow skin tones of the entire breast when compared to baseline measurements before WBI (p < 0.001) and a significant increase of cutis, subcutis, and oedema thickness (p < 0.001, p < 0.001, and p = 0.004, respectively). At follow-up, there were no significant differences in either pigmentation changes or skin fibrosis between the Hydrofilm and standard of care breast halves. Conclusion: These data suggest that Hydrofilm can be safely used in the context of acute RD prevention, without affecting late side effects, supporting its widespread use. Full article

Background: This study aims to assess the benefit of a deep inspiration breath hold (DIBH) over the standard irradiation technique, and eventually to identify anatomical and/or treatment preplanning characteristics correlated with the LAD dose. Methods: Patients with left-sided breast cancer undergoing whole breast radiotherapy with DIBH were analyzed. All patients included in the analysis had plans in DIBH and free-breathing (FB). Receiving operating characteristics (ROC analysis) were used to identify the cut-off point of parameters to predict the LAD maximum dose > 10 Gy and LAD mean dose > 4 Gy, and the areas under the curve (AUCs) were computed. Post-test probability has been performed to evaluate the effect of parameters’ combination. Results: One hundred ninety-seven patients were analyzed. The LAD dose was significantly reduced in DIBH plans with the maximum and mean dose reduced by 31.7% (mean value 3.5 Gy vs. 4.8 Gy, p ≤ 0.001) and 28.1% (mean value 8.2 Gy vs. 12.8 Gy, p ≤ 0.001) in DIBH plans compared to FB plans. The strongest predictor of the LAD dose (maximum > 10 Gy and mean > 4 Gy) was the minimum distance of LAD from tangent open fields. Other parameters were lung volume and heart volume (LAD Dmax > 10 Gy) and lung volume, heart volume, and breast separation (LAD Dmean > 4 Gy). Conclusion: The dosimetric advantage of DIBH is clear in all patients and DIBH should always be preferred. Full article

Background: The management of cancer relapse in previously irradiated tissues is a challenging therapeutic issue. The aim of this work was to report our experience with breast reirradiation for locoregionally recurrent breast cancer. Methods: All patients who underwent breast or chest wall in-field reirradiation at the Institut Curie, Paris, France, between 2003 and 2019, were identified. Efficacy outcomes and physician-reported toxicities were retrospectively assessed. Results: A total of 21,372 patients underwent breast irradiation in our institution. Of these, 28 received a second course of radiotherapy to the homolateral breast/chest wall. A total of 18 (64%) patients were treated with a curative intent, and 10 (36%) were treated for palliative purposes. Only one acute and one late grade 3 adverse events were reported. One patient with major cardiovascular risk factors died of myocardial infarction 13 months after left breast reirradiation. The 2-year LRFS, OS, DSS, PFS and MFS were 59%, 79%, 82%, 46% and 75%, respectively, in the whole cohort. The 2-year LRFS (72% vs. 31%, p = 0.02), OS (94% vs. 50%, p < 0.01), DSS (94% vs. 56%, p < 0.01) and PFS (61% vs. 20%, p = 0.02) differed significantly between patients treated with curative or palliative intent but not the MFS (78% vs. 69%, p = 0.77). Among the patients, eight (29%) remained relapse-free 5 years after reirradiation. Conclusion: Breast/chest wall reirradiation appears to be feasible with good disease control, especially in patients treated with a curative intent, and presents acceptable toxicity rates. Full article

Background: Multiple randomized trials have established adjuvant endocrine therapy (ET) and whole breast irradiation (WBI) as the standard approach after breast-conserving surgery (BCS) in early-stage breast cancer. The omission of WBI has been studied in multiple trials and resulted in reduced local control with maintained survival rates and has therefore been adapted as a treatment option in selected patients in several guidelines. Omitting ET instead of WBI might also be a valuable option as both treatments have distinctly different side effect profiles. However, the clinical outcomes of BCS + ET vs. BCS + WBI have not been formally analyzed. Methods: We performed a systematic literature review searching for randomized trials comparing BCS + ET vs. BCS + WBI in low-risk breast cancer patients with publication dates after 2000. We excluded trials using any form of chemotherapy, regional nodal radiation and mastectomy. The meta-analysis was performed using a two-step process. First, we extracted all available published event rates and the effect sizes for overall and breast-cancer-specific survival (OS, BCSS), local (LR) and regional recurrence, disease-free survival, distant metastases-free interval, contralateral breast cancer, second cancer other than breast cancer and mastectomy-free interval as investigated endpoints and compared them in a network meta-analysis. Second, the published individual patient data from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) publications were used to allow a comparison of OS and BCSS. Results: We identified three studies, including a direct comparison of BCS + ET vs. BCS + WBI (n = 1059) and nine studies randomizing overall 7207 patients additionally to BCS only and BCS + WBI + ET resulting in a four-arm comparison. In the network analysis, LR was significantly lower in the BCS + WBI group in comparison with the BCS + ET group (HR = 0.62; CI-95%: 0.42–0.92; p = 0.019). We did not find any differences in OS (HR = 0.93; CI-95%: 0.53–1.62; p = 0.785) and BCSS (OR = 1.04; CI-95%: 0.45–2.41; p = 0.928). Further, we found a lower distant metastasis-free interval, a higher rate of contralateral breast cancer and a reduced mastectomy-free interval in the BCS + WBI-arm. Using the EBCTCG data, OS and BCSS were not significantly different between BCS + ET and BCS + WBI after 10 years (OS: OR = 0.85; CI-95%: 0.59–1.22; p = 0.369) (BCSS: OR = 0.72; CI-95%: 0.38–1.36; p = 0.305). Conclusion: Evidence from direct and indirect comparison suggests that BCS + WBI might be an equivalent de-escalation strategy to BCS + ET in low-risk breast cancer. Adverse events and quality of life measures have to be further compared between these approaches. Full article