This study investigates objective long-term cosmetic outcomes in patients with breast cancer after intraoperative radiotherapy applied as a boost (IORT boost) from a pooled international cohort. A pooled analysis of two prospective studies with IORT boost (low-energy X‑rays, 20 Gy; inclusion criteria: 3.5 cm maximum tumor size and preoperative indication for a boost according to local criteria) during breast-conserving surgery followed by whole-breast radiotherapy (46–50 Gy). The analysis included photos from a subgroup of the prospective phase IV TARGeted Intraoperative radioTherapy (TARGIT) Boost Quality Registry (BQR) study (NCT01440010) with a follow-up of up to 10 years as well as patients from a Swiss study (ROKSM; Spital Thurgau AG; NCT02114086) with a follow-up of 5 years. The pooled analysis included photos from both trials taken at the same timepoints (6 weeks, 6 months, 1 year, 2 years, and 5 years after completion of whole-breast radiotherapy). Cosmetic results were evaluated with the validated BCCT.core software (BCCT.core 2.0, INESC Porto, Portugal) to assess symmetry, color, and scars. A generalized estimating equation (GEE) regression model was used to compare the two cohorts over time. The pooled analysis included 777 cosmetic assessments from 276 patients. Across all follow-ups in the pooled analysis, the majority of cosmetic results were rated as excellent or good (61.9

Whole-breast radiotherapy (WBRT) after breast-conserving surgery (BCS) in older patients can be challenging due to the increased presence of comorbidities, comedication, the presence of a pacemaker or difficulties in traveling to treatment every day. Challenging times, such as the pandemic, can also lead to RT not being performed despite the indication. Very short treatment regimens are therefor of special interest in this population reducing overall treatment time and radiation exposure. TARGIT-E is a phase II trial investigating intraoperative radiotherapy (IORT) during BCS in elderly patients. We report long-term follow-up results of TARGIT-E. Patients with BC (≥ 70 years, cT1-2, cN0, M0) were enrolled at 28 European centers. A single dose of IORT (20 Gy) was given during BCS. Additional postoperative WBRT was applied if risk factors were present in final histopathology. Primary outcome was local recurrence-free rate (RFR) using the Kaplan–Meier-method. Late toxicities were assessed by LENT-SOMA criteria, and cosmetic outcomes were graded using BCCT.core software. In 591 patients (median follow-up 5.4 years) RFR was 97.6

The TARGIT BQR (boost quality registry) phase IV trial investigates clinical outcomes of breast cancer patients with standard external-beam radiotherapy (EBRT) of the whole breast and intraoperative radiotherapy (IORT) with low-kV x‑rays as an anticipated tumor bed boost in a real-world setting. Intraoperative radiotherapy was performed immediately after breast-conserving surgery in one fraction. External-beam radiotherapy and systemic treatment were given according to the German S3 guideline for breast cancer and local tumor board recommendations. Outcome parameters were death, local recurrence, metastasis, local lymph node recurrence, and ipsilateral and contralateral invasive breast cancer. Kaplan–Meier estimates were used to calculate overall survival, metastasis-free survival, local recurrence-free survival, and disease-free survival. From 10 centers, 1133 patients were recruited. This analysis included 871 patients with 879 cancers, with a median follow-up of 36 months (up to 12 years). An IORT boost was performed in 82

Background: Cancer remains the second most common cause of death in Germany. Performance management and specialization concepts in medicine have the potential to positively influence the care and chances of survival of patients. Objective: From the perspective of the University Hospital Freiburg (UKF), the legislative initiative within the framework of the Hospital Treatment Improvement Act (KHVVG) results in a number of medical strategic implications. This article explains and discusses the background, objectives and contents of the reform project "Occasional surgical oncology" and provides perspectives on strategic fields of action. Material and methods: Analysis and interpretation of the draft of the Act for improvement of the treatment quality in hospitals and on the reform of the remuneration structures (Federal Government draft act). Results: From the point of view of the UKF hospitals should engage in cooperative discussions with neighboring hospitals at the earliest opportunity to shape regional healthcare with the goals of mapping the local allocation of oncology patients for optimal treatment, mitigating the loss of patients at affected locations and preparing for patient growth at facilities that will continue to provide treatment in surgical oncology. Discussion: The ongoing legislative process and the fact that a reliable analysis of relevant treatment areas will be possible for hospitals in the first half of 2025, presents particular challenges for hospitals and the strategic planning of activities. The gaps in the bill presented in this article should be urgently addressed to avoid undermining the project's goals and to support the hospitals remaining in the healthcare system in their preparations.

The integration of artificial intelligence (AI) into oncology promises a revolution in diagnosis, treatment, and research. Various applications are considered, with a focus on stress and burnout experienced by oncologists. The potentials are comprehensively discussed, starting from prevention through wearables and AI-assisted analysis of health data to personalized treatment planning and accelerated drug development. One area of focus is AlphaFold, an AI application for protein folding. The management of patient data and the creation of medical reports are optimized by AI, with search engines and large language models (LLM) playing a prominent role. The increasing specialization of LLMs, particularly in medical text generation, underscores their growing importance. The feasibility of AI applications is emphasized, addressing the need for resources and training for medical personnel. Commercial organizations, such as DeepMind, play a crucial role in implementing AI in clinical practice. Regulatory challenges are discussed, including data privacy, quality control, liability, and ethical aspects. The European Health Data Space (EHDS) is a promising initiative for promoting secure data exchange within the European Union. Overall, AI can facilitate significant advancements in oncology. However, regulatory challenges require careful attention to ensure an ethically responsible and safe implementation. AI applications have the potential to improve cancer care, revolutionize patient management, and reduce the workload for medical personnel.

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.

e14003 Background: Gadopiclenol (Elucirem, Guerbet, France) is a new high relaxivity macrocyclic gadolinium-based contrast agent (GBCA), recently approved by the FDA and EMA at the dose of 0.05 mmol/kg. The aim of this post-hoc analysis was to evaluate the impact of contrast-enhanced MRI with gadopiclenol at 0.1 mmol/kg on decision making and radiotherapy (RT) treatment planning of brain metastases (BM). Methods: This is a post-hoc analysis of data from a phase IIb study where patients underwent two separate MRI examinations, one with gadopiclenol at 0.025, 0.05, 0.1 or 0.2 mmol/kg and one with gadobenate dimeglumine at 0.1 mmol/kg. MR images of patients who received both GBCAs at 0.1 mmol/kg, with ≥1 BM detected in either of the scans, were subjected to a blinded reader analysis and contouring by two radiation oncology experts. For each patient, treatment plans (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]) were determined for both MRIs, with the gross target volume (GTV) indicating the contrast-enhancing aspects of the tumor. Mean GTVs and normal tissue volumes receiving 12 Gy (V 12 ), as well as the Dice similarity coefficient (DSC) were obtained for the paired contours. The Spearman´s rank (ρ) correlation was additionally calculated. Furthermore, three experts blindly evaluated the contrast enhancement of each lesion for contouring purposes and subjectively qualified them as “better”, in detriment of the counterpart, or “equal”. Results: In total, images from 13 adult patients were analyzed. MRI with gadopiclenol depicted additional BM as compared with gadobenate dimeglumine in 7 patients (54%). The treatment plan was changed in 2 patients (15%), from no treatment to SRS and from SRS to WBRT. Gadopiclenol depicted additional BM in these 2 patients (from 0 and 10 BM with gadobenate dimeglumine to 1 and 15 BM with gadopiclenol). The mean GTVs and V 12 were comparable between gadopiclenol and gadobenate dimeglumine (p=0.694, p=1.974). The mean DSC was 0.70 (SD: 0.14, ρ0.82). From a total of 36 answers, contrast enhancement was qualified as better with gadopiclenol in 21 (58.3%) evaluations, better with gadobenate dimeglumine in 8 (22.2%) evaluations, while no difference was observed in 7 (19.4%) evaluations. Conclusions: Gadopiclenol at 0.1 mmol/kg improved BM detection and contrast enhancement with potential impact on RT treatment decisions.

PDF file 154K, S7: Correlation analysis of expression of miR-217, miR-218 and their respective targets RIN2, EFNB2, and DUSP5 in tumor tissue with various clinicopathological features

Background: Intraoperative radiotherapy can serve as an anticipated boost (IORT boost) in combination with a subsequent external whole breast irradiation in high-risk breast cancer patients and is part of many guidelines. Nevertheless, there are only few prospective data available regarding cosmetic outcome after IORT boost using kV X-rays. The aim of this study was to evaluate the cosmetic outcome of patients treated within the prospective phase IV TARGeted Intraoperative radioTherapy (TARGIT) Boost Quality Registry (BQR) study (NCT01440010) in one center.Methods: In the context of the TARGIT BQR study standardized photos in three positions (arms down, arms up, from the side) were available for different time points. For this analysis a layperson, a radiation oncologist and a gynecologist evaluated available photos at different time points during follow-up with up to 4 years using the Harvard scale (comparison of treated and the untreated breast; rating: excellent, good, fair, poor). Longitudinal results were compared to preoperative results (baseline).Results: Seventy-three patients were available for the analysis. Baseline cosmetic assessment was excellent/ good in 98.8% (mean value for all three positions). Postoperative cosmetic outcome (median) was good for all positions and remained constant for 4 years. Around 30% of the patients showed a constant or even improved cosmetic outcome compared to baseline. Only few patients showed a poor result at 4 years. The majority of patients showed an excellent or good cosmetic outcome at all time points.Conclusions: Patients from the prospective TARGIT BQR study treated with IORT boost and additional whole breast irradiation showed good or excellent cosmetic outcomes in most cases during 4 years of followup. These results add important information for shared decision making in breast cancer patients.

PurposeTo compare the late toxicity profile of hypofractionation and normofractionation for whole-breast radiotherapy in breast cancer (BC) patients after conserving surgery.MethodsSixty-year-old or older patients with pTis-pT3, pN0-pN1a, M0 BC were recruited and stratified to hypofractionated (arm R-HF) or normofractionated (arm L-NF) intensity-modulated radiotherapy (IMRT), for right- and left-sided BC, respectively, in this single-center, non-randomized, non-inferiority trial. A boost was allowed if indicated. The primary outcome was the cumulative percentage of patients developing grade III fibrosis, grade I telangiectasia, and/or grade II hyperpigmentation after 2 years, with a pre-specified non-inferiority margin of 15% increase from an expected 2-year toxicity rate of 20%.ResultsThe Median follow-up was 4.93 (0.57–8.65) years for R-HF and 5.02 (0.65–8.72) years for L-NF (p=0.236). The median age was 68 (60–83 and 60–80) years, respectively. In total, 226 patients were recruited (107 for R-HF and 119 for L-NF), with 100 and 117 patients suitable for assessment, respectively. A boost was delivered in 51% and 53% of each arm, respectively. Median PTV volumes were 1013.6 (273–2805) cm3 (R-HF) and 1058.28 (315–2709) cm3 (L-NF, p=0.591). The 2-year primary endpoint rate was 6.1% (95% CI 1.3-11.7, n=5 of 82) and 13.3% (95% CI 7-20.2, n=14 of 105), respectively (absolute difference -7.2%, one-sided 95% CI ∞ to -0.26, favoring R-HF). No local recurrence-free- or overall-survival differences were found.ConclusionIn this prospective non-randomized study, hypofractionation did not have higher toxicity than normofractionated whole-breast IMRT.

Abstract Background Although glioblastoma (GB) is associated with a devastating prognosis, a small proportion of patients achieve long-term survival rates. We herein present a matched-pair analysis of molecular factors found in long- and short-term survivors (LTS, STS). Methods We performed a cross-institutional analysis of 262 patient records and matched a group of 91 LTS (≥ 3 years) with two groups of STS (STS-1, n = 91; STS-2, n = 80). Matching was performed according to age, Karnofsky Performance Status, initial therapy and adjuvant therapy. Molecular factors were compared between LTS (total of 91 patients) v. STS-1, and LTS (subgroup of 80 patients) v. STS-2. We included glial fibrillary acidic protein (GFAP), O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, isocitrate dehydrogenase 1 (IDH-1); furthermore, the proliferation index was analyzed (Ki-67/MIB-1). Results IDH-1 and decreased Ki-67 were numerically associated with LTS but the difference was only significant compared to STS-1 (n.s. v. STS-2). LTS was associated with MGMT promoter hypermethylation (p = 0.013 and p = 0.022) and GFAP expression (p < 0.001 and p = 0.001). Positivity for both factors combined compared to negativity for one factor occurred more often in the LTS group (p = 0.002 and p = 0.006); negativity for both factors combined did not occur in the LTS group. Conclusion In this retrospective analysis, GFAP expression and MGMT promoter methylation were associated with LTS. Given the hypothesis-generating nature of our study, these observations should be confirmed in prospective clinical trials.

BACKGROUND:Postoperative stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (hFSRT) to tumor cavities is emerging as a new standard of care after resection of brain metastases. Both Gamma Knife (GK) and CyberKnife (CK) are modalities commonly used for stereotactic radiotherapy, but fractional schemes are not consistent. The objective of this study was to evaluate outcomes in patients receiving postoperative stereotactic radiotherapy of resected brain metastases (BM) using different fractionation schedules and modalities in two large centers.METHODS:Patients with newly diagnosed BM who underwent postoperative SRS or hFSRT with either GK or CK at two large cancer centers were retrospectively evaluated. We analyzed local control (LC), regional control (RC) and overall survival (OS).RESULTS:From April 14th to May 18th, 2020, 79 patients with 81 resection cavities were treated. Forty-seven patients (59.5%) received GK and 32 patients (40.5%) received CK treatment. Fifty-four cavities (66.7%) were treated with hFSRT and 27 (33.3%) with SRS. The most common hFSRT and SRS scheme was 3x10 Gy and 1x16 Gy, respectively. Median OS was 11.7 months with survival rates of 44.7% at 1 year and 18.5% at 2 years. LC was 83.3% after 1 year. Median time to regional progression was 12.0 months with RC rates of 61.1% at 6 months and 41.0% at 12 months. There was no difference in OS, LC or RC between GK and CK treatments or SRS and hFSRT.CONCLUSIONS:Both SRS and hFSRT provide high local control rates in resected BM regardless of the applied modality.