Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases.

BACKGROUND: Trials evaluating the omission of completion axillary-lymph-node dissection in patients with clinically node-negative breast cancer and sentinel-lymph-node metastases have been compromised by limited statistical power, uncertain nodal radiotherapy target volumes, and a scarcity of data on relevant clinical subgroups. METHODS: We conducted a noninferiority trial in which patients with clinically node-negative primary T1 to T3 breast cancer (tumor size, T1, ≤20 mm; T2, 21 to 50 mm; and T3, >50 mm in the largest dimension) with one or two sentinel-node macrometastases (metastasis size, >2 mm in the largest dimension) were randomly assigned in a 1:1 ratio to completion axillary-lymph-node dissection or its omission (sentinel-node biopsy only). Adjuvant treatment and radiation therapy were used in accordance with national guidelines. The primary end point was overall survival. We report here the per-protocol and modified intention-to-treat analyses of the prespecified secondary end point of recurrence-free survival. To show noninferiority of sentinel-node biopsy only, the upper boundary of the confidence interval for the hazard ratio for recurrence or death had to be below 1.44. RESULTS: Between January 2015 and December 2021, a total of 2766 patients were enrolled across five countries. The per-protocol population included 2540 patients, of whom 1335 were assigned to undergo sentinel-node biopsy only and 1205 to undergo completion axillary-lymph-node dissection (dissection group). Radiation therapy including nodal target volumes was administered to 1192 of 1326 patients (89.9%) in the sentinel-node biopsy-only group and to 1058 of 1197 (88.4%) in the dissection group. The median follow-up was 46.8 months (range, 1.5 to 94.5). Overall, 191 patients had recurrence or died. The estimated 5-year recurrence-free survival was 89.7% (95% confidence interval [CI], 87.5 to 91.9) in the sentinel-node biopsy-only group and 88.7% (95% CI, 86.3 to 91.1) in the dissection group, with a country-adjusted hazard ratio for recurrence or death of 0.89 (95% CI, 0.66 to 1.19), which was significantly (P<0.001) below the prespecified noninferiority margin. CONCLUSIONS: The omission of completion axillary-lymph-node dissection was noninferior to the more extensive surgery in patients with clinically node-negative breast cancer who had sentinel-node macrometastases, most of whom received nodal radiation therapy. (Funded by the Swedish Research Council and others; SENOMAC ClinicalTrials.gov number, NCT02240472.).

International multidisciplinary consensus on the integration of radiotherapy with new systemic treatments for breast cancer: European Society for Radiotherapy and Oncology (ESTRO)-endorsed recommendations.

Novel systemic therapies for breast cancer are being rapidly implemented into clinical practice. These drugs often have different mechanisms of action and side-effect profiles compared with traditional chemotherapy. Underpinning practice-changing clinical trials focused on the systemic therapies under investigation, thus there are sparse data available on radiotherapy. Integration of these new systemic therapies with radiotherapy is therefore challenging. Given this rapid, transformative change in breast cancer multimodal management, the multidisciplinary community must unite to ensure optimal, safe, and equitable treatment for all patients. The aim of this collaborative group of radiation, clinical, and medical oncologists, basic and translational scientists, and patient advocates was to: scope, synthesise, and summarise the literature on integrating novel drugs with radiotherapy for breast cancer; produce consensus statements on drug-radiotherapy integration, where specific evidence is lacking; and make best-practice recommendations for recording of radiotherapy data and quality assurance for subsequent studies testing novel drugs.

Atlas-based auto-segmentation for delineating the heart and cardiac substructures in breast cancer radiation therapy.

BACKGROUND: This study aimed to develop and validate an automatic multi-atlas segmentation method for delineating the heart and substructures in breast cancer radiation therapy (RT). MATERIAL AND METHODS: The atlas database consisted of non-contrast-enhanced planning CT scans from 42 breast cancer patients, each with one manual delineation of the heart and 22 cardiac substructures. Half of the patients were scanned during free-breathing, the rest were scanned during a deep inspiration breath-hold. The auto-segmentation was developed in the MIM software system and validated geometrically and dosimetrically in two steps: The first validation in a small dataset to ensure consistency of the atlas. This was succeeded by a final test where multiple manual delineations in CT scans of 12 breast cancer patients were compared to the auto-segmentation. For geometric evaluation, the dice similarity coefficient (DSC) and the mean surface distance (MSD) were used. For dosimetric evaluation, the RT doses to each substructure in the manual and the automatic delineations were compared. RESULTS: In the first validation, a high geometric and dosimetric performance between the automatic and manual delineations was observed for all substructures. The final test confirmed a high agreement between the automatic and manual delineations for the heart (DSC = 0.94) and the cardiac chambers (DSC: 0.75-0.86). The difference in MSD between the automatic and manual delineations was low (<4 mm) in all structures. Finally, a high correlation between mean RT doses for the automatic and the manual delineations was observed for the heart and substructures. CONCLUSIONS: An automatic segmentation tool for delineation of the heart and substructures in breast cancer RT was developed and validated with a high correlation between the automatic and manual delineations. The atlas is pivotal for large-scale evaluations of radiation-associated heart disease.

Prevention, Detection, and Management of Heart Failure in Patients Treated for Breast Cancer.

PURPOSE OF REVIEW: Long-term survival has increased significantly in breast cancer patients, and cardiovascular side effects are surpassing cancer-related mortality. We summarize risk factors, prevention strategies, detection, and management of cardiotoxicity, with focus on left ventricular dysfunction and heart failure, during breast cancer treatment. RECENT FINDINGS: Baseline treatment of cardiovascular risk factors is recommended. Anthracycline and trastuzumab treatment constitute a substantial risk of developing cardiotoxicity. There is growing evidence that this can be treated with beta blockers and angiotensin antagonists. Early detection of cardiotoxicity with cardiac imaging and circulating cardiovascular biomarkers is currently evaluated in clinical trials. Chest wall irradiation accelerates atherosclerotic processes and induces fibrosis. Immune checkpoint inhibitors require consideration for surveillance due to a small risk of severe myocarditis. Cyclin-dependent kinases4/6 inhibitors, cyclophosphamide, taxanes, tyrosine kinase inhibitors, and endocrine therapy have a lower-risk profile for cardiotoxicity. Preventive and management strategies to counteract cancer treatment-related left ventricular dysfunction or heart failure in breast cancer patients should include a comprehensive cardiovascular risk assessment and individual clinical evaluation. This should include both patient and treatment-related factors. Further clinical trials especially on early detection, cardioprevention, and management are urgently needed.

The clinical database and implementation of treatment guidelines by the Danish Breast Cancer Cooperative Group in 2007-2016.

BACKGROUND: Since 40 years, Danish Breast Cancer Cooperative Group (DBCG) has provided comprehensive guidelines for diagnosis and treatment of breast cancer. This population-based analysis aimed to describe the plurality of modifications introduced over the past 10 years in the national Danish guidelines for the management of early breast cancer. By use of the clinical DBCG database we analyze the effectiveness of the implementation of guideline revisions in Denmark. METHODS: From the DBCG guidelines we extracted modifications introduced in 2007-2016 and selected examples regarding surgery, radiotherapy (RT) and systemic treatment. We assessed introduction of modifications from release on the DBCG webpage to change in clinical practice using the DBCG clinical database. RESULTS: Over a 10-year period data from 48,772 patients newly diagnosed with malignant breast tumors were entered into DBCG's clinical database and 42,197 of these patients were diagnosed with an invasive carcinoma following breast conserving surgery (BCS) or mastectomy. More than twenty modifications were introduced in the guidelines. Implementations, based on prospectively collected data, varied widely; exemplified with around one quarter of the patients not treated according to a specific guideline within one year from the introduction, to an almost immediate full implantation. CONCLUSIONS: Modifications of the DBCG guidelines were generally well implemented, but the time to full implementation varied from less than one year up to around five years. Our data is registry based and does not allow a closer analysis of the causes for delay in implementation of guideline modifications.

The potential benefits from respiratory gating for breast cancer patients regarding target coverage and dose to organs at risk when applying strict dose limits to the heart: results from the DBCG HYPO trial.

PURPOSE: The potential benefits from respiratory gating (RG) compared to free-breathing (FB) regarding target coverage and dose to organs at risk for breast cancer patients receiving post-operative radiotherapy (RT) in the DBCG HYPO multicentre trial are reported. MATERIAL AND METHODS: Patients included in the DBCG HYPO trial were randomized between 50 Gy in 25 fractions (normofractionated) versus 40 Gy in 15 fractions (hypofractionated). A tangential forward field-in-field dose planning technique was used to cover the clinical target volume (CTV) with the intent to limit dose to the left anterior descending coronary artery (LADCA) to 20 Gy and 17 Gy in the normo- and hypofractionated arms, respectively. Treatment plan data for 1327 patients from four Danish centres was retrospectively analyzed. FB right-sided patients served as control group for the left-sided patients regarding CTV V95% (relative volume receiving at least 95% of the prescribed dose), mean heart dose (MHD) and mean lung dose (MLD). RESULTS: Median CTV V95% was for FB right-sided, FB left-sided and RG left-sided patients 94.6, 92.6 and 94.7% for normofractionated therapy, respectively, and 94.6, 91.8 and 94.4% for hypofractionated therapy and did not differ significantly for RG left-sided plans compared to FB right-sided in either study arm. CTV V95% was significantly lower for FB versus RG for left-sided plans in both arms. Median MHD was 0.7, 1.8 and 1.5 Gy (normofractionated therapy) versus 0.6, 1.5 and 1.2 Gy (hypofractionated therapy), respectively. The corresponding median MLD was 9.0, 8.3 and 7.3 Gy versus 7.3, 6.4 and 5.8 Gy, respectively. CONCLUSIONS: RG for left-sided breast cancer patients ensured similar CTV V95% as for FB right-sided patients. MLD was lower for RG due to the increased lung volume. MHD was generally low due to strict protocol-defined maximum dose to LADCA, but for left-sided patients RG led to significantly lower MHD.

The 2016 Assisi Think Tank Meeting on breast cancer: white paper.

PURPOSE: To identify weak points in daily routine use of radiation therapy (RT) for non-metastatic breast cancer patients, particularly when data are lacking or equivocal, a "think tank" of experts met in Assisi. METHODS: Before the meeting, controversial issues on non-metastatic breast cancer were identified and reviewed, and clinical practice investigated by means of an online questionnaire. During the 3-day meeting, topics were discussed in-depth with attendees and potential sponsors that are involved in breast cancer treatment. RESULTS: Three issues were identified as needing further investigation: (1) Regional lymph node treatment in early-stage breast cancer; (2) Combined post-mastectomy RT and breast reconstruction; (3) RT in patients treated with primary systemic therapy. Future research proposals included the following: (1) Participating in appropriately selected on-going clinical trials; (2) Designing new randomized controlled clinical trials and prospective population cohort studies; (3) Setting-up large database(s) to generate predictive response models and detect biomarkers for tailored loco-regional treatments. CONCLUSIONS: It is hoped that the ATTM findings, as described in the present white paper, will stimulate a new generation of radiation oncologists to focus on research in these areas, and that the white paper will become a tool for multidisciplinary groups to help them design research proposals and strategies.

Importance of margin width in breast-conserving treatment of early breast cancer.

BACKGROUND AND METHOD: The association between margin width and ipsilateral breast tumour recurrence (IBTR, defined as invasive recurrence) was investigated in a population-based nationwide cohort of 11,900 patients undergoing breast-conserving therapy for invasive cancer. RESULTS: The median follow-up was 4.9 years. The cumulative incidence of IBTR at 5 and 9 years was 2.4% and 5.9%, respectively. A final positive margin increased the risk of IBTR (HR 2.51; 95% CI 1.02-6.23). No decrease in IBTR with a wider negative margin compared to a narrow but negative margin was observed in the adjusted analysis of margin width (>0 to <2 mm vs. ≥2 to <5 mm vs. ≥5 mm (reference): HR 1.54 (CI 95% 0.81-2.93) vs. 0.95 (CI 95% 0.56-1.62) vs. 1). However, few patients had narrow margins. The factors associated with increased IBTR were young age (P < 0.001), >4 positive lymph nodes (P = 0.008) and re-excision (P = 0.003). A reduced risk of IBTR was observed with chemotherapy (P < 0.001), boost radiation (P = 0.023) and ER positivity (P < 0.001). CONCLUSION: An overall low rate of IBTR was observed. A final positive margin was associated with a more than twofold risk of IBTR. There was no evidence for better local control with wider margins, but the data were insufficient to show whether narrow margins were as good as wider negative margins in terms of local control. J. Surg. Oncol. 2016;113:609-615. © 2016 Wiley Periodicals, Inc.

Pattern of relapse after breast conserving therapy, a study of 1519 early breast cancer patients treated in the Central Region of Denmark 2000-2009.

BACKGROUND: The continuous improvements in diagnosing and treatment of breast cancer are reflected in the ever changing pattern of recurrence. The aim of the study was to investigating recurrence pattern and prognostic factors of recurrence in a population-based cohort. MATERIAL AND METHOD: In total 1519 consecutive patients treated with breast conserving therapy (BCT) for invasive carcinoma between 2000 and 2009 in the Central Region of Denmark was included. Patients received adjuvant irradiation and systemic treatment according to the guidelines of the Danish Breast Cancer Cooperative Group, including boost for young women and those with a narrow margin. RESULTS: Median follow-up was 5.3 years (range 0.3-14.4). In total 183 women experienced breast cancer recurrence, 44 ipsilateral breast cancer recurrence, 13 regional recurrences, and 126 distant metastasis (DM). This corresponds to a cumulative risk of DM as first event at five and nine years of 6.5% and 12.6%, respectively. Further 42 women developed breast cancer in the contralateral breast. Disease-free survival (DFS) at five and nine years was 88% and 76%, respectively. Large tumor size (>20 mm), lymph node involvement, and vascular invasion were significantly associated with increased risk of DM. Margin width and age were not associated with risk of DM. CONCLUSION: Acceptable recurrence rates and DFS were observed. Patients with large tumors, lymph node involvement, and vascular invasion had an increased risk of DM.

The Influence of Repeat Surgery and Residual Disease on Recurrence After Breast-Conserving Surgery: A Danish Breast Cancer Cooperative Group Study.

BACKGROUND: A significant proportion of women who have breast-conserving surgery (BCS) subsequently undergo re-excision or proceed to mastectomy. This study aimed to identify factors associated with residual disease after repeat surgery and to determine their effect on ipsilateral breast tumor recurrence (IBTR) and survival. METHODS: The study cohort was identified within the national population-based registry of the Danish Breast Cancer Cooperative Group, including women who underwent BCS for unilateral invasive breast cancer between 2000 and 2009. RESULTS: The study investigated 12,656 women. Within 2 months after initial BCS, 1342 (11 %) of these women had a re-excision, and 756 (6 %) of the women had a mastectomy. Residual disease was found in 20 % of re-excisions and 59 % of mastectomies. In adjusted analysis, ductal carcinoma in situ (DCIS) outside the invasive tumor, positive initial margin, and age younger than 50 years were associated with increased risk of residual disease. In the adjusted analysis, patients with residual disease after re-excision had an increased risk of IBTR regardless whether residual findings were invasive carcinoma [hazard ratio (HR), 2.97; 95 % confidence interval (CI) 1.57-5.62] or DCIS (HR, 2.58; 95 % CI 1.50-4.45). However, no difference was seen in overall survival comparing patients receiving one excision with those having repeat surgery with or without residual disease (p = 0.96). CONCLUSION: A higher risk of IBTR seen after re-excision was associated with residual disease. Overall survival was similar regardless of repeat surgery and residual findings.

CT-planned internal mammary node radiotherapy in the DBCG-IMN study: benefit versus potentially harmful effects.

BACKGROUND: The DBCG-IMN is a nationwide population-based cohort study on the effect of internal mammary node radiotherapy (IMN-RT) in patients with node positive early breast cancer. Due to the risk of RT-induced heart disease, only patients with right-sided breast cancer received IMN-RT, whereas patients with left-sided breast cancer did not. At seven-year median follow-up, a 3% gain in overall survival with IMN-RT has been reported. This study estimates IMN doses and doses to organs at risk (OAR) in patients from the DBCG-IMN. Numbers needed to harm (NNH) if patients with left-sided breast cancer had received IMN-RT are compared to the number needed to treat (NNT). MATERIAL AND METHODS: Ten percent of CT-guided treatment plans from the DBCG-IMN patients were selected randomly. IMNs and OAR were contoured in 68 planning CT scans. Dose distributions were re-calculated. IMNs and OAR dose estimates were compared in right-sided versus left-sided breast cancer patients. In six left-sided patients, IMN-RT was simulated, and OAR doses were compared to those in the original plan. The NNH resulting from the change in mean heart dose (MHD) was calculated using a published model for risk of RT-related ischemic heart death. RESULTS: In original plans, the absolute difference between right- and left-sided V90% to the IMNs was 38.0% [95% confidence interval (5.5%; 70.5%), p < 0.05]. Heart doses were higher in left-sided plans. With IMN-RT simulation without regard to OAR constraints, MHD increased 4.8 Gy (0.9 Gy; 8.7 Gy), p < 0.05. Resulting NNHs from ischemic heart death were consistently larger than the NNT with IMN-RT. CONCLUSION: Refraining from IMN-RT on the left side may have spared some ischemic heart deaths. Assuming left-sided patients benefit as much from IMN-RT as right-sided patients, the benefits from IMN-RT outweigh the costs in terms of ischemic heart death.

Author's response to Letter-to-the-Editor from Chang JS. concerning: "Benefit of respiratory gating in the Danish Breast Cancer Group partial breast irradiation trial".

We appreciate Chang JS.'s interest in the article: "Benefit of respiratory gating in the Danish Breast Cancer Group partial breast irradiation trial". The author's response corroborates the statements and comments of Chang JS.

Increased Microvascular Filtration and Vascular Endothelial Growth Factor-D associated with Changed Lymphatic Vessel Morphology in Breast Cancer Treated Patients.

Background: Vascular endothelial growth factors (VEGF) and inflammatory cytokines are indicated to be implicated in lymphedema development. We aimed to describe changes in microvascular filtration and VEGFs in a patient cohort vulnerable to breast cancer-related lymphedema development correlated with data on lymphatic morphology and function. Methods: Consecutive node-positive breast cancer patients operated in the axilla and evaluated approximately 12 months after adjuvant locoregional radiotherapy were studied. Capillary filtration rate (CFR) and isovolumetric pressure of the arms were measured by strain gauge plethysmography, and 13 blood proteins were quantified by Luminex and Elisa technology in 28 patients and 18 healthy controls. Results: The CFR was reduced in both arms from baseline to 1-year follow-up (ipsilateral: P = 0.016 and contralateral: P = 0.001). When stratifying lymphatic complications (morphologic abnormalities and/or breast cancer-related lymphedema), CFR reached a lower steady-state in the arms with normal morphology (I:P = 0.013 and C:P = 0.013) whereas the ipsilateral arm with lymphatic complications remained unchanged (P = 0.457). In patients with lymphatic abnormal vessels, the levels of VEGF-D were 86% higher than in patients with normal lymphatic vessels (P = 0.042), whereas levels of VEGFR-3 were 64% higher (P = 0.016). Conclusions: Through one year of follow-up, CFR did not decrease in the lymphatic complicated treated arms as observed in noncomplicated treated arms. The patients had increased levels of VEGF-D and VEGFR-3. This correlation suggests that VEGF plays a role in the appearance of subcutaneous abnormal lymphatic vessels in the treated arms, which also maintain a fluid filtration/drainage mismatch up to one year after breast cancer treatment.

Benefit of respiratory gating in the Danish Breast Cancer Group partial breast irradiation trial.

BACKGROUND AND PURPOSE: Partial breast irradiation (PBI)has beenthe Danish Breast Cancer Group(DBCG) standard for selected breast cancer patients since 2016 based onearlyresults from the DBCG PBI trial.During trial accrual, respiratory-gated radiotherapy was introduced in Denmark. This study aims to investigate the effect of respiratory-gating on mean heart dose (MHD). PATIENTS AND METHODS: From 2009 to 2016 the DBCG PBI trial included 230 patientswith left-sided breast cancer receiving external beam PBI, 40 Gy/15 fractions/3 weeks.Localization of the tumor bed on the planning CT scan, the use of respiratory-gating, coverage of the clinical target volume (CTV), and doses to organs at risk were collected. RESULTS: Respiratory-gating was used in 123 patients (53 %). In 176 patients (77 %) the tumor bed was in the upper and in 54 patients (23 %) in the lower breast quadrants. The median MHD was 0.37 Gy (interquartile range 0.26-0.57 Gy), 0.33 Gy (0.23-0.49 Gy) for respiratory-gating, and 0.49 Gy (0.31-0.70 Gy) for free breathing, p < 0.0001. MHD was < 1 Gy in 206 patients (90 %) and < 2 Gy in 221 patients (96 %). Respiratory-gating led to significantly lower MHD for upper-located, but not for lower-located tumor beds, however, all MHD were low irrespective of respiratory-gating. Respiratory-gating did not improve CTV coverage or lower lung doses. CONCLUSIONS: PBI ensured a low MHD for most patients. Adding respiratory-gating further reduced MHD for upper-located but not for lower-located tumor beds but did not influence target coverage or lung doses. Respiratory-gating is no longer DBCG standard for left-sided PBI.

Breast induration and irradiated volume in the DBCG HYPO trial: The impact of age, smoking, and boost.

PURPOSE: To investigate the association between irradiated breast volume and grade 2-3 breast induration three years after radiotherapy in the phase III Danish Breast Cancer Group HYPO trial randomizing patients ≥ 41 years to whole breast irradiation (WBI) with 40 Gy/15fr versus 50 Gy/25fr. METHODS: Treatment plans were available for all Danish patients. Associations between frequency of induration and irradiated volume, age, smoking status, and boost were assessed by logistic regression. A sequential boost was given to patients < 50 years or in case of a narrow (<2 mm) resection margin. RESULTS: RT plans from 1,333 patients were analyzed with 178 (13 %) having grade 2-3 induration. 1135 patients had only WBI. For this group, induration was correlated with irradiated breast volume for patients ≥ 65 years (n = 343, 10 %/22 % for small/large irradiated volumes, p = 0.005) but not for patients aged 50-64 years (n = 792, 11 % for both small and large volumes, p = 0.82). Smoking doubled the frequency irrespective of irradiated volume and age. All patients < 50 years (n = 156) had a boost. A volume effect was found for this group (5 %/21 % induration for small/large volume, p = 0.002). 42 patients ≥ 50 years had a boost and 14 (33 %) had grade 2-3 induration, however, with a p-value > 0.05 due to the few numbers of patients. CONCLUSION: A relationship between irradiated breast volume and 3-year frequency of breast induration was found for patients ≥ 65 years, whilst not for patients aged 50-64 years. Smoking doubled the risk of induration irrespective of volume and age. A dose-induration relationship was seen for boost patients < 50 years.

EUSOMA quality indicators for non-metastatic breast cancer: An update.

INTRODUCTION: Quality care in breast cancer is higher if patients are treated in a Breast Center with a dedicated and specialized multidisciplinary team. Quality control is an essential activity to ensure quality care, which has to be based on the monitoring of specific quality indicators. Eusoma has proceeded with the up-dating of the 2017 Quality indicators for non-metastatic breast cancer based on the new diagnostic, locoregional and systemic treatment modalities. METHODS: To proceed with the updating, EUSOMA setup a multidisciplinary working group of BC experts and patients' representatives. It is a comprehensive set of QIs for early breast cancer care, which are classified as mandatory, recommended, or observational. For the first time patient reported outcomes (PROMs) have been included. As used in the 2017 EUSOMA QIs, evidence levels were based on the short version of the US Agency for Healthcare Research and Quality. RESULTS: This is a set of quality indicators representative for the different steps of the patient pathway in non-metastatic setting, which allow Breast Centres to monitor their performance with referring standards, i.e minimum standard and target. CONCLUSIONS: Monitoring these Quality Indicators, within the Eusoma datacentre will allow to have a state of the art picture at European Breast Centres level and the development of challenging research projects.

Essential requirements for reporting radiation therapy in breast cancer clinical trials: An international multi-disciplinary consensus endorsed by the European Society for Radiotherapy and Oncology (ESTRO).

The European Society for Radiotherapy and Oncology (ESTRO) has advocated the establishment of guidelines to optimise precision radiotherapy (RT) in conjunction with contemporary therapeutics for cancer care. Quality assurance in RT (QART) plays a pivotal role in influencing treatment outcomes. Clinical trials incorporating QART protocols have demonstrated improved survival rates with minimal associated toxicity. Nonetheless, in routine clinical practice, there can be variability in the indications for RT, dosage, fractionation, and treatment planning, leading to uncertainty. In pivotal trials reporting outcomes of systemic therapy for breast cancer, there is limited information available regarding RT, and the potential interaction between modern systemic therapy and RT remains largely uncharted. This article is grounded in a consensus recommendation endorsed by ESTRO, formulated by international breast cancer experts. The consensus was reached through a modified Delphi process and was presented at an international meeting convened in Florence, Italy, in June 2023. These recommendations are regarded as both optimal and essential standards, with the latter aiming to define the minimum requirements. A template for a case report form (CRF) has been devised, which can be utilised by all clinical breast cancer trials involving RT. Optimal requirements include adherence to predefined RT planning protocols and centralised QART. Essential requirements aim to reduce variations and deviations from the guidelines in RT, even when RT is not the primary focus of the trial. These recommendations underscore the significance of implementing these practices in both clinical trials and daily clinical routines to generate high-quality data.

6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7).

This manuscript describes the Advanced Breast Cancer (ABC) international consensus guidelines updated at the last two ABC international consensus conferences (ABC 6 in 2021, virtual, and ABC 7 in 2023, in Lisbon, Portugal), organized by the ABC Global Alliance. It provides the main recommendations on how to best manage patients with advanced breast cancer (inoperable locally advanced or metastatic), of all breast cancer subtypes, as well as palliative and supportive care. These guidelines are based on available evidence or on expert opinion when a higher level of evidence is lacking. Each guideline is accompanied by the level of evidence (LoE), grade of recommendation (GoR) and percentage of consensus reached at the consensus conferences. Updated diagnostic and treatment algorithms are also provided. The guidelines represent the best management options for patients living with ABC globally, assuming accessibility to all available therapies. Their adaptation (i.e. resource-stratified guidelines) is often needed in settings where access to care is limited.

Quality assurance of conventional non-CT-based internal mammary lymph node irradiation in a prospective Danish Breast Cancer Cooperative Group trial: the DBCG-IMN study.

UNLABELLED: In 2003, the Danish Breast Cancer Cooperative Group (DBCG) initiated DBCG-IMN, a prospective study on the effect of adjuvant internal mammary lymph node radiotherapy (IMN-RT) in patients with early lymph node positive breast cancer (BC). In the study, standard DBCG IMN-RT was provided only to patients with right-sided BC. We provide estimates of doses to IMNs and organs at risk (OARs) in patients treated with the non-CT-based RT techniques used during the DBCG-IMN study. MATERIAL AND METHODS: Five DBCG RT regimens were simulated on planning CT scans from 50 consecutively scanned BC patients, 10 in each group. Intended target volumes were chest wall or breast and regional lymph nodes ± IMNs. Field planning was conducted in the Eclipse(TM) RT treatment planning system. Subsequently, IMN clinical target volumes (CTVs) and OARs were delineated. Estimates on doses to the IMN-CTV and OARs were made. RESULTS: IMN dose coverage estimates were consistently higher in right-sided techniques where IMN treatment was intended (p < 0.0001). Estimated doses to cardiac structures were low regardless of whether IMNs were treated or not. Post-lumpectomy patients had the highest estimated lung doses. CONCLUSION: Overall, simulator-based treatment using the DBCG RT techniques resulted in satisfactory coverage of IMNs and acceptable levels of OAR irradiation.

Delineation of target volumes and organs at risk in adjuvant radiotherapy of early breast cancer: national guidelines and contouring atlas by the Danish Breast Cancer Cooperative Group.

UNLABELLED: During the past decade planning of adjuvant radiotherapy (RT) of early breast cancer has changed from two-dimensional (2D) to 3D conformal techniques. In the planning computerised tomography (CT) scan both the targets for RT and the organs at risk (OARs) are visualised, enabling an increased focus on target dose coverage and homogeneity with only minimal dose to the OARs. To ensure uniform RT in the national prospective trials of the Danish Breast Cancer Cooperative Group (DBCG), a national consensus for the delineation of clinical target volumes (CTVs) and OARs was required. MATERIAL AND METHODS: A CT scan of a breast cancer patient after surgical breast conservation and axillary lymph node (LN) dissection was used for delineation. During multiple dummy-runs seven experienced radiation oncologists contoured all CTVs and OARs of interest in adjuvant breast RT. Two meetings were held in the DBCG Radiotherapy Committee to discuss the contouring and to approve a final consensus. The Dice similarity coefficient (DSC) was used to evaluate the delineation agreement before and after the consensus. RESULTS: The consensus delineations of CTVs and OARs are available online and a table is presented with a contouring description of the individual volumes. The consensus provides recommendations for target delineation in a standard patient both in case of breast conservation or mastectomy. Before the consensus, the average value of the DSC was modest for most volumes, but high for the breast CTV and the heart. After the consensus, the DSC increased for all volumes. CONCLUSION: The DBCG has provided the first national guidelines and a contouring atlas of CTVs and OARs definition for RT of early breast cancer. The DSC is a useful tool in quantifying the effect of the introduction of guidelines indicating improved inter-delineator agreement. This consensus will be used by the DBCG in our prospective trials.