Iridium Kankernetwerk

Abstract Background: In early-stage breast cancer, surgical de-escalation from axillary lymph node dissection (ALND) to sentinel lymph node biopsy (SLNB) did not compromise oncologic safety. This has led to the realization that SLNB predominantly provides prognostic information and may itself not influence recurrence or survival. The BOOG 2013-08 trial was therefore designed to evaluate whether omission of SLNB in clinically T1-2N0 patients treated with breast-conserving surgery and whole-breast irradiation (summarized together as BCT) is safe with respect to regional recurrence rates (RR) and distant disease-free survival (DDFS). Methods: The BOOG 2013-08 (NCT02271828) is a multicenter, non-inferiority, randomized phase-3 trial including women with unilateral cT1-2N0 breast cancer treated with BCT. Clinically node-negative was based on negative findings on physical examination and preoperative axillary ultrasound (including negative cyto- or histopathology in case of a suspicious findings). The trial was conducted in the Netherlands between 2015 and 2022 across 25 centers. Patients were randomized (1:1) to SLNB or omission of SLNB. Randomization was stratified by clinical tumor size (<3 cm vs ≥3 cm), histological grade (grade I-II vs III), hormone receptor status (HR), HER2 status, age (≤50, 50 ≤ 75, >75 years), primary systemic therapy (PST) and participating center. The primary endpoint was 5-year RR; secondary endpoints as presented here were 3-year RR and DDFS. Cumulative probabilities of RR and DDFS were estimated using the Kaplan-Meier method. Non-inferiority was defined as an absolute difference in RR ≤5% in favor of the control group at 5 years. Analyses were performed per-protocol. Results: A total of 1,733 patients were enrolled across 25 centers. After excluding 159 patients (n=106 due to radiation therapy protocol violations), 1574 patients were included (SLNB: n=749; no-SLNB: n=825). At the time of analysis, 100% of patients had reached 3 years and 73% 5-year follow-up. Median follow-up was 5.0 years (range 0.78-6.86, IQR 1.94). Mean age was 61.5 years, 83% had cT1 tumors and 17% cT2 tumors. Tumor grade was I in 28.7%, II in 54.1% and III in 17.2%. Breast cancer subtype was HR+HER2- in 86.8%, triple negative in 5.8% and HER2+ in 7.4% of patients. In the SLNB arm, micro- and macrometastatic disease was detected in 6.0% and 7.7%, respectively. Preliminary data at a median 5-year follow-up showed that the estimated probability of RR was 0.5% in the SLNB arm (95% CI 0.0-1.1) and 1.2% in the no-SLNB arm (95% CI 0.4-2.0), corresponding to an absolute difference of 0.7% (95% CI -0.3 to 1.7). The confidence interval ranges from -0.3 to 0.7, indicating that the 5% non-inferiority margin is not exceeded. Five-year DDFS was 98.3% (95% CI 97.3-99.3) in the SLNB arm versus 96.1% (95% CI 94.5-97.7) in the no-SLNB arm (log-rank p=0.071).Chemo- or endocrine therapy was administered in 11.3% of patients as PST (12.3% SLNB arm vs. 10.3 no-SLNB arm, p=0.214). In total, 50.0% of patients received systemic therapy (51.2% SLNB vs. 49.0% no-SLNB, p 0.202). Of these 50.0%, 39.4% received chemotherapy with or without targeted therapy. Among ER-positive patients, adjuvant endocrine therapy was administered in 48.6% (SLNB) and 46.6% (no-SLNB), p=0.732, while chemotherapy was given in 9.8% and 8.2%, respectively (p=0.532). Conclusions: In cT1-2N0 breast cancer patients treated with BCT, omission of SLNB resulted in a non-inferior median 5-year RR and DDFS compared with SLNB. These premature findings support the omission of SLNB, at least in case of cT1N0, ER+, grade 1-2 breast cancer. This study further demonstrates that adjuvant hormonal therapy should not be a prerequisite for omission of the SLNB. Citation Format: R. J. Schipper, L. M. van Roozendaal, V. M. Wintraecken, J. M. Simons, M. Moossdorff, E. J. T. Luiten, F. van Duijnhoven, L. de Munck, L. F. C. Dols, R. Koelemij, R. van Eekeren, A. B. Francken, T. van Dalen, K. Keymeulen, J. Volders, J. A. van der Hage, H. Torrenga, P. A. Neijenhuis, P. Nijhuis, D. van Uden, E. Heuts, M. A. Bessems, C. D. Dirksen, M. H. Martens, M. F. Bouwmeester, K. Schenk, A. V. R. J. Bell, S. Maaskant-Braat, L. J. A. Strobbe, S. C. Linn, P. M. P. Poortmans, M. L. G. Vane, V. C. G. Tjan-Heijnen, K. K. B. T. van der Vijver, M. B. I. Lobbes, J. de Vries, L. Emelianova-Hiddink, J. Kandt, L. J. Boersma, J. H. W. de Wilt, S. M. J. van Kuijk, M. L. Smidt, BOOG 2013-08 Study Group. Omission of sentinel lymph node biopsy in clinically T1-2 node-negative breast cancer patients treated with breast-conserving therapy: results of the Dutch BOOG 2013-08 randomized controlled trial after a median follow-up of 5 years [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr GS2-11.

Results from the EMBARK trial reshape the treatment paradigm for high-risk biochemical recurrence of prostate cancer. EMBARK data support the use of androgen receptor pathway inhibitors combined with metastasis-directed therapy in a personalized, multidisciplinary care approach for this subset of patients.

This study aimed to investigate global practice patterns, barriers, and physician perspectives on implementing ultra-hypofractionated radiation therapy (UHF-RT) in breast cancer treatment. A 19-question online survey, distributed to radiation oncologists worldwide between February and August 2025, assessed UHF adoption, clinical use, barriers, training, and outlook. Chi-square tests compared adoption by institutional type, economic context, and physician experience (p < 0.05). 89 responses from 24 countries were analyzed. Moderate hypofractionation (MHF) predominated (70.8%), followed by UHF (20.2%). Overall, 80.9% had applied UHF, mainly for breast-only cases. Reported barriers included lack of clinical guidelines (49.2%), insufficient training (20.3%), equipment limitations (18.6%), and reimbursement issues (16.9%). No significant differences in adoption were found, though trends showed higher use in academic centers and high-income countries. UHF is increasingly adopted worldwide, yet MHF remains predominant. Standardizing education, infrastructure, and reimbursement policies could support wider global use.

Abstract BACKGROUND Positron emission tomography (PET) is increasingly used in patients with brain tumors, yet its adoption varies across institutions. METHODS To assess the current landscape, a cross-sectional survey was conducted among European Organization for Research and Treatment of Cancer (EORTC) – Brain Tumour Group (BTG) sites between June 2024 and August 2024. RESULTS Out of the 312 sites invited, 103 replies from 20 countries in the Europe/Middle East region were received. PET availability was reported by 96/103 (93.2%) sites, of whom 74 reported PET use in patients with brain tumors. Most frequently, PET was performed in glioma (69/74, 93.2%), followed by brain metastasis (58/74, 78.4%), meningioma (52/74, 70.3%), and CNS lymphoma (46/74, 62.2%). Amino acid PET was used at 62/71 centers (87.3%), mainly in glioma (58/59, 98.3%) and for differentiation of tumor progression from treatment-related changes (58/59, 98.3%), differential diagnosis (54/59, 91.5%), and hotspot delineation (47/59, 79.7%). Somatostatin receptor (SSTR) PET was performed at 50/68 sites (73.5%), predominantly in meningioma (48/49, 98.0%), and for patient selection before radioligand therapy (41/49, 83.7%) as well as for target volume definition in radiotherapy (33/49, 67.3%) and differential diagnosis (27/49, 55.1%). PET was covered by statutory health insurance at 46/59 (78.0%) centers for amino acid PET and 33/49 (67.3%) for SSTR PET according to self-reported information. Main reasons for not performing PET in clinical routine included limited availability of tracers (14/29, 48.3%), high cost (11/29, 37.9%), and PET considered unnecessary by referring physicians (8/29, 27.6%). CONCLUSION PET is widely used among EORTC-BTG sites, although implementation varies and is influenced by factors such as tracer availability, cost, and institutional perceptions. While further data from broader surveys including non-academic institutions is needed, the findings support the implementation of PET as clinical trial endpoint.

BackgroundPatients with pancreatic ductal adenocarcinoma face a poor prognosis, with radical resection being the only potential cure. Because symptoms typically appear late, many patients are diagnosed with advanced disease. Locally advanced pancreatic tumours are characterised by extensive vascular involvement, which precludes R0 resection. Systemic therapy is therefore indicated, not only for palliation but also for reducing the risk of metastatic disease. Locoregional control remains paramount, irrespective of distant metastases as progressive tumours can cause considerable morbidity, negatively affecting patients’ quality of life. Previous studies investigating conventionally fractionated (chemo)radiotherapy have yielded mixed results, indicating opportunities for further research to optimise treatment outcomes. The TORPEDO study aims to prospectively assess whether adding stereotactic body radiation therapy (SBRT) to standard chemotherapy can improve outcomes in patients with initially inoperable, non-metastasized pancreatic ductal adenocarcinoma.MethodsThis study is a multicentre randomised phase II trial. While it primarily targets locally advanced lesions, patients with borderline resectable tumours who are either medically inoperable or decline surgery are also eligible. After twelve weeks of induction chemotherapy (modified FOLFIRINOX or gemcitabine/nab-paclitaxel), patients without development of distant metastases are randomised 1:1 to receive either continued chemotherapy alone (arm A) or one month of chemotherapy followed by SBRT (5 × 8 Gy) (arm B). Resectability is evaluated through a multidisciplinary tumour board. The primary endpoint is the 2-year progression-free survival. Secondary endpoints include overall survival, local progression-free survival, metastasis-free survival, objective response rate, resectability, R0 resection rates, surgical morbidity, toxicity, quality of life, and the impact of radiation doses on outcomes.DiscussionWe evaluate the efficacy and safety of SBRT following induction chemotherapy in patients with inoperable, non-metastasized pancreatic ductal adenocarcinoma. We hypothesize that adding SBRT enhances outcome by improving local control and increasing overall survival. Effective control of the pancreatic primary tumor may help reduce pain and thereby improve quality of life.Trial registrationThe ethics committee of the GZA Hospitals approved this study on April 8, 2024. It was registered on ClinicalTrials.gov (NCT06691425) on November 15, 2024.

A growing number of cancer patients with brain metastases can benefit from stereotactic radiosurgery (SRS) thanks to recent advances in systemic therapies which have led to improved survival. Meanwhile, selection criteria for SRS treatments are evolving to include patients with increasingly many metastases. With an increasing patient load, single-isocenter treatments on widely available C-arm linear accelerators are an attractive option. However, the planning of such treatments is challenging for multi-target cases due to the island blocking problem, which occurs when the multi-leaf collimator cannot conform to all targetssimultaneously. We propose a multi-target partitioning algorithm that mitigates excessive exposure of normal tissue caused by the island blockingproblem. The proposed algorithm considers an initial set of arc trajectories and divides (partitions) the set of targets per trajectory into smaller subsets to treat with separate back-and-forth arc passes, simultaneously optimizing both the target subsets and collimator angles to minimize island blocking. We incorporated this algorithm into a fully automated treatment planning script and evaluated it on 20 simulated patient cases, each with 10 brain metastases and 21Gy prescriptions. For each case, the script generated a series of volumetric modulated arc therapy (VMAT) plans with increasingly many arcs along the three trajectories. Each such plan was compared to four baseline plans generated with alternative heuristics for distributing targets across arcs. We also evaluated the algorithm retrospectively on six clinicalcases. Partitioning significantly improved the gradient index (GI), global efficiency index ( ) and brain compared to simultaneous treatment of all metastases. For example, the average GI improved from 5.9 to 3.3, from 0.32 to 0.46, and normal brain from 49 to 26 between 3 and 9 arcs. The baseline plans improved similarly, but the proposed algorithm was significantly better at utilizing a limited budget of arcs. All target partitioning strategies increased the total number of monitor units (MUs). The dose gradient in single-isocenter VMAT plans can be substantially improved by treating a smaller subset of metastases at a time. This requires more MUs and arcs, implying a trade-off between delivery time and plan quality, which can be explored using the algorithm proposed in thispaper.

Abstract Patients with oestrogen receptor-positive (ER+), HER2-negative, early breast cancer (BC) have low pathological complete response (pCR) rates following neoadjuvant chemotherapy (NACT). Phase 3 trials showed that adding an anti-PD-1 immune checkpoint inhibitor (ICI) improves pCR, but there was less benefit in the PD-L1 negative tumours, characterised by an immune “cold” tumour microenvironment (TME). We hypothesized that immune-modulating stereotactic body radiation therapy (iSBRT) could enhance treatment response by reprogramming the immune deprived TME in early ER+/HER2- BC. We further proposed that adding an anti-CD73 antibody could reduce adenosine-mediated immunosuppression and increase efficacy. We conducted a phase 2, randomized, multicentre trial (Neo-CheckRay) evaluating NACT plus iSBRT, with or without durvalumab (anti-PD-L1) and with or without oleclumab (anti-CD73) in 147 patients with high-risk, early, ER+/HER2- BC. In the intention-to-treat (ITT) population, primary endpoint Residual Cancer Burden (RCB) 0 or 1 was achieved in 35.4% of patients receiving iSBRT + NACT alone (No_ICI), 45.1% in the Single_ICI arm, and 47.9% in the Double_ICI arm (p=0.203). Secondary endpoint pCR rates were 16.7%, 29.4%, and 33.3% (p=0.059), respectively. In the predefined per-protocol population, which included only MammaPrint High-Risk patients (n=131), the secondary endpoint pCR was met: 16.3% in No_ICI and 35.6% in Double_ICI (p=0.040). Among PD-L1-negative patients (n=91), pCR rates were 3.4% (No_ICI), 28.1% (Single_ICI), and 30.3% (Double_ICI). In contrast, no significant differences between treatment arms were observed in PD-L1-positive patients. Whole-transcriptome analysis revealed low expression of immune signatures at baseline in PD-L1-negative patients, while biopsies 1 week after iSBRT indicated TME reprogramming toward an inflamed phenotype with iSBRT + ICI. In conclusion, iSBRT combined with NACT and anti-PD-L1 significantly improves pCR in PD-L1-negative, ER+/HER2- BC, suggesting a novel strategy for immune-cold tumours. Clinical trials.gov identifier: NCT03875573.