Thijs van Dalen

This study examined gene expression profile (GEP) use in relation to reimbursement policies and chemotherapy administration, both for patients with and without GEP indication. Women aged ≥ 18–69 years and diagnosed with early‐stage breast cancer between January 2011 and June 2024 were selected from the Netherlands Cancer Registry. GEP use in relation to reimbursement policies and GEP result in relation to chemotherapy administration was analysed using flowcharts and a trend line. For patients with GEP indication, logistic regression analyses were conducted to determine if the reimbursement periods influenced the GEP use, and GEP use was analysed per region in the Netherlands and incidence year using trend lines. In total, 138,765 patients were included. Among 17,525 patients with GEP indication, proportions of patients who received a GEP were higher during retrospective reimbursement (25%) and publicly known reimbursement (37%) compared with no reimbursement (9%) and differed across regions in the Netherlands. Proportions of patients who did not receive chemotherapy were higher for patients who had a low‐risk MammaPrint (93%) or Oncotype DX (97%) result compared with patients who had a high‐risk MammaPrint (17%) or Oncotype DX (15%) result. Among 13,003 patients with GEP indication who did not receive GEP, 52% did receive chemotherapy. Approximately one‐third of patients who met GEP criteria and were eligible for publicly known reimbursement received a GEP. Appropriate follow‐up steps and further research seem required to analyse reasons for not ordering a GEP in times of reimbursement, since GEP results help chemotherapy decision‐making.

This phase II study compared radiofrequency ablation, microwave ablation, and cryoablation for early-stage breast cancer, demonstrating that cryoablation achieved the highest complete ablation rate with no complications, supporting its selection for a phase III trial.

Background: The non-inferiority randomized controlled trial BOOG 2013-08 investigates the oncological safety and impact on health-related quality of life (HRQoL) of sentinel lymph node biopsy (SNLB) omission in cT1–2 N0 breast cancer. The primary aim of the present study was to compare patient-reported arm function and HRQoL up to 3 years after study inclusion in cT1–2 N0 patients with breast cancer undergoing breast-conserving surgery (BCS) with or without SLNB. The secondary aim was to explore the association between personality traits ‘trait anxiety’ and ‘neuroticism’, and perceived arm function and HRQoL. Methods: A total of 1733 women with unilateral cT1–2 N0 invasive breast cancer treated with BCS with or without SLNB were included. The primary outcomes of arm function (assessed using the Lymphoedema Functioning, Disability, and Health Questionnaire) and HRQoL (assessed using the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR-23 questionnaires) were analysed. Results: Analyses included 821 patients (383 with SLNB and 438 without SLNB). Those in the SLNB group experienced a slight, temporary decline in arm function (P < 0.025) and reported more HRQoL arm and breast symptoms (P < 0.049). High trait anxiety or neuroticism was associated with significant poorer arm function and lower HRQoL. Conclusion: SLNB slightly reduced arm function, temporarily affecting HRQoL arm and breast symptoms. Neuroticism significantly negatively impacted arm function and HRQoL. Measuring and stratifying for personality traits is crucial for interpreting patient-reported outcomes and to identify patients needing additional support after surgery. Registration number: NCT02271828 (http://www.clinicaltrials.gov).

Purpose: As life expectancy continues to rise, post-treatment health-related quality of life (HRQoL) of breast cancer patients becomes increasingly important. This study examined the one-year longitudinal relation between axillary treatments and physical, psychosocial, and sexual wellbeing and arm symptoms. Methods: Women diagnosed with breast cancer who received different axillary treatments being axilla preserving surgery (APS) with or without axillary radiotherapy or full axillary lymph node dissection (ALND) with or without axillary radiotherapy were included. HRQoL was assessed at baseline, 6- and 12-months postoperatively using the BREAST-Q and the European Organization for Research and Treatment of Cancer QoL Questionnaire Breast Cancer Module (EORTC QLQ-BR23). Mixed regression models were constructed to assess the impact of axillary treatment on HRQoL. HRQoL at baseline was compared to HRQoL at 6- and at 12-months postoperatively. Results: In total, 552 patients were included in the mixed regressions models. Except for ALND with axillary radiotherapy, no significant differences in physical and psychosocial wellbeing were found. Physical wellbeing decreased significantly between baseline and 6- and 12-months postoperatively (p < 0.001, p = 0.035) and psychosocial wellbeing decreased significantly between baseline and 12 months postoperatively (p = 0.028) for ALND with axillary radiotherapy compared to APS alone. Arm symptoms increased significantly between baseline and 6 months and between baseline and 12 months postoperatively for APS with radiotherapy (12.71, 13.73) and for ALND with radiotherapy (13.93, 16.14), with the lowest increase in arm symptoms for ALND without radiotherapy (6.85, 7.66), compared to APS alone (p < 0.05). Conclusion: Physical and psychosocial wellbeing decreased significantly for ALND with radiotherapy compared to APS alone. Shared decision making and expectation management pre-treatment could be strengthened by discussing arm symptoms per axillary treatment with the patient.

Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular sarcoma with variable aggressive clinical behavior. In this retrospective study, we aimed to investigate prognostic factors based on clinicopathologic findings in a molecularly/immunohistochemically confirmed nationwide multicenter cohort of 57 EHE cases. Patients had unifocal disease (n = 29), multifocal disease (n = 5), lymph node metastasis (n = 8) and/or distant metastasis (n = 15) at the time of diagnosis. The overall survival rate was 71.4% at 1 year and 50.7% at 5 years. Survival did not correlate with sex, age or histopathological parameters. No survival differences were observed between multifocal and metastatic disease, suggesting that multifocality represents early metastases and treatment options are limited in comparison to unifocal disease. In unifocal tumors, survival could be predicted using the risk stratification model of Shibayama et al., dividing the cases into low- (n = 4), intermediate- (n = 15) and high- (n = 3) risk groups. No clinical or histopathological parameters were associated with progressive unifocal disease course. Lymph node metastases at the time of diagnosis occurred in 14.0% of the cases and were mainly associated with tumor localization in the head and neck area, proposing lymph node dissection. In conclusion, our results demonstrate the aggressive behavior of EHE, emphasize the prognostic value of a previously described risk stratification model and may provide new insights regarding tumor focality, therapeutic strategies and prognosis.

Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular sarcoma with variable aggressive clinical behavior. In this retrospective study we aimed to investigate prognostic factors based on clinicopathologic findings in a molecular/immunohistochemical confirmed nationwide multicenter cohort of 57 EHE. Patients had unifocal disease (n=29), multifocal disease (n=5), lymph node metastasis (n=8) and/or distant metastasis (n=15) at the time of diagnosis. The overall survival rate was 69.6% at 1 year and 50.5% at 5 years. Survival did not correlate with sex, age or histo-pathological parameters. No survival differences were observed between multifocal and metastatic disease suggesting that multifocality represents early metastases and treatment options are limited in comparison to unifocal disease. In unifocal tumors, survival could be predicted using the risk stratification model of Shibayama et al. dividing the cases into low (n=4), intermediate (n=15) and high (n=3) risk-groups. Larger tumor size (>3cm) and higher mitotic count (>1/10HPF) was asso-ciated with progressive unifocal disease course. Lymph node metastases at time of diagnosis oc-curred in 14.0% of the cases and was mainly associated with tumor localization in the head and neck area proposing lymph node dissection. In conclusion, our results demonstrate the aggressive behavior of EHE, emphasize the prognostic value of a previous described risk stratification model and may provide new insights regarding tumor focality, therapeutic strategies and prognosis.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. PURPOSE: The European Organisation for Research and Treatment of Cancer 10981-22023 AMAROS trial evaluated axillary lymph node dissection (ALND) versus axillary radiotherapy (ART) in patients with cT1-2, node-negative breast cancer and a positive sentinel node (SN) biopsy. At 5 years, both modalities showed excellent and comparable axillary control, with significantly less morbidity after ART. We now report the preplanned 10-year analysis of the axillary recurrence rate (ARR), overall survival (OS), and disease-free survival (DFS), and an updated 5-year analysis of morbidity and quality of life. METHODS: In this open-label multicenter phase III noninferiority trial, 4,806 patients underwent SN biopsy; 1,425 were node-positive and randomly assigned to either ALND (n = 744) or ART (n = 681). RESULTS: Per intention-to-treat analysis, 10-year ARR cumulative incidence was 0.93% (95% CI, 0.18 to 1.68; seven events) after ALND and 1.82% (95% CI, 0.74 to 2.94; 11 events) after ART (hazard ratio [HR], 1.71; 95% CI, 0.67 to 4.39). There were no differences in OS (HR, 1.17; 95% CI, 0.89 to 1.52) or DFS (HR, 1.19; 95% CI, 0.97 to 1.46). ALND was associated with a higher lymphedema rate in updated 5-year analyses (24.5% v 11.9%; P < .001). Quality-of-life scales did not differ by treatment through 5 years. Exploratory analysis showed a 10-year cumulative incidence of second primary cancers of 12.1% (95% CI, 9.6 to 14.9) after ART and 8.3% (95% CI, 6.3 to 10.7) after ALND. CONCLUSION: This 10-year analysis confirms a low ARR after both ART and ALND with no difference in OS, DFS, and locoregional control. Considering less arm morbidity, ART is preferred over ALND for patients with SN-positive cT1-2 breast cancer.