Real-world survival of Danish patients with HER2-positive metastatic breast cancer.

BACKGROUND: The purpose was to investigate the treatment flow of patients with HER2-positive metastatic breast cancer (mBC), progression-free survival (PFS) and overall survival (OS) across treatment lines and adherence to guidelines (defined as trastuzumab, pertuzumab and chemotherapy first line, where 85% received vinorelbine as backbone and T-DM1 second line). Furthermore, we identified clinical markers to predict the risk of developing brain metastases. MATERIAL AND METHODS: Patients with HER2-positive mBC, diagnosed between 01.01.2014-31.12.2019, registered in the database of the Danish Breast Cancer Group were included in this real-word study. Clinical follow-up was assessed until 01.10.2020 and complete follow-up for overall survival until 01.10.2021. Survival data were analyzed using the Kaplan-Meier method with guidelines adherence analyzed as a time-varying covariate, and the risk of CNS metastasis was estimated by the cumulative incidence function. RESULTS: 631 patients were included. 329 (52%) patients followed the guidelines. The median OS for all patients was 42.3 months (95% Cl, 38.2-48.4), and significantly higher for the patients who followed guidelines; NA (95% CI, 78.2-NA). The median PFS for all patients was 13.4 months (95% Cl, 12.1-14.8), 6.6 (95% Cl, 5.8-7.6) and 5.8 (95% Cl, 4.9-6.9) for first, second and third line of treatment, respectively. Patients with ER-negative mBC had a higher risk of developing brain metastases and patients with high tumor burden had a higher risk of developing brain metastases with an adjusted HR of 0.69 (95% CI, 0.49-0.98), p = 0.047 and 2.69 (95% CI, 1.45-5.00), p = 0.002, respectively. CONCLUSION: We found that only half of the patients with HER2-positive mBC, received first and second-line treatment according to national guidelines. Patients receiving treatment according to guidelines had a significantly higher median OS compared to patients who did not. We also found that patients with ER-negative disease or high tumor burden had a significantly higher risk of developing brain metastases.

Evaluating Danish Breast Cancer Group locoregional radiotherapy guideline adherence in clinical treatment data 2008-2016: The DBCG RT Nation study.

BACKGROUND AND PURPOSE: Guideline adherence in radiotherapy is crucial for maintaining treatment quality and consistency, particularly in non-trial patient settings where most treatments occur. The study aimed to assess the impact of guideline changes on treatment planning practices and compare manual registry data accuracy with treatment planning data. MATERIALS AND METHODS: This study utilised the DBCG RT Nation cohort, a collection of breast cancer radiotherapy data in Denmark, to evaluate adherence to guidelines from 2008 to 2016. The cohort included 7448 high-risk breast cancer patients. National guideline changes included, fractionation, introduction of respiratory gating, irradiation of the internal mammary lymph nodes, use of the simultaneous integrated boost technique and inclusion of the Left Anterior Descending coronary artery in delineation practice. Methods for structure name mapping, laterality detection, detection of temporal changes in population mean lung volume, and dose evaluation were presented and applied. Manually registered treatment characteristic data was obtained from the Danish Breast Cancer Database for comparison. RESULTS: The study found immediate and consistent adherence to guideline changes across Danish radiotherapy centres. Treatment practices before guideline implementation were documented and showed a variation among centres. Discrepancies between manual registry data and actual treatment planning data were as high as 10% for some measures. CONCLUSION: National guideline changes could be detected in the routine treatment data, with a high degree of compliance and short implementation time. Data extracted from treatment planning data files provides a more accurate and detailed characterisation of treatments and guideline adherence than medical register data.

Development and comprehensive evaluation of a national DBCG consensus-based auto-segmentation model for lymph node levels in breast cancer radiotherapy.

BACKGROUND AND PURPOSE: This study aimed at training and validating a multi-institutional deep learning (DL) auto segmentation model for nodal clinical target volume (CTVn) in high-risk breast cancer (BC) patients with both training and validation dataset created with multi-institutional participation, with the overall aim of national clinical implementation in Denmark. MATERIALS AND METHODS: A gold standard (GS) dataset and a high-quality training dataset were created by 21 BC delineation experts from all radiotherapy centres in Denmark. The delineations were created according to ESTRO consensus delineation guidelines. Four models were trained: One per laterality and extension of CTVn internal mammary nodes. The DL models were tested quantitatively in their own test-set and in relation to interobserver variation (IOV) in the GS dataset with geometrical metrics, such as the Dice Similarity Coefficient (DSC). A blinded qualitative evaluation was conducted with a national board, presented to both DL and manual delineations. RESULTS: A median DSC > 0.7 was found for all, except the CTVn interpectoral node in one of the models. In the qualitative evaluation 'no corrections needed' were acquired for 297 (36 %) in the DL structures and 286 (34 %) for manual delineations. A higher rate of 'major corrections' and 'easier to start from scratch' was found in the manual delineations. The models performed within the IOV of an expert group, with two exceptions. CONCLUSION: DL models were developed on a national consensus cohort and performed on par with the IOV between BC experts and had a comparable or higher clinical acceptance than expert manual delineations.

Neoadjuvant chemotherapy and HER2 dual blockade including biosimilar trastuzumab (SB3) for HER2-positive early breast cancer: Population based real world data from the Danish Breast Cancer Group (DBCG).

BACKGROUND: Dual blockade with trastuzumab and pertuzumab combined with neoadjuvant chemotherapy (NACT) has been increasingly used for HER2-positive tumours >2 cm and/or with positive axillary lymph nodes in order to evaluate pathologic response and obtain better surgical management. SB3 is a registered biosimilar trastuzumab approved following a phase III trial demonstrating similar efficacy in the neoadjuvant setting as trastuzumab. However, the study was done without pertuzumab. METHOD: The database of the Danish Breast Cancer Group was used to extract data on all patients who started NACT with SB3 and pertuzumab between September 1, 2018 and August 31, 2019. The primary endpoint was pathological complete response (pCR) rate. RESULTS: In total 215 patients received NACT and dual blockade. The median age was 55 (24-81). NACT used was cyclophosphamide and epirubicin followed by weekly paclitaxel (62% on six cycles, 35% on eight cycles) or other chemotherapy followed by weekly paclitaxel (3%). Overall, 56% of patients achieved pCR. 60 of 88 node-positive patients pre-NACT achieved ypN0(i-) after neoadjuvant treatment. pCR rate was significantly associated with estrogen receptor status and malignancy grade. An association with CEP17/HER2-ratio was assessed. CONCLUSION: Real world data on dual blockade with SB3 and pertuzumab in combination with NACT in a nationwide population-based study show a pCR rate comparable to that seen in previous clinical studies.