SLK-Kliniken Heilbronn

Abstract Background: Current data support that metastatic hormone receptor-positive (HR+) and HER2-positive (HER2+) breast cancer offers distinct treatment options targeting both the hormone receptor and the HER2-pathway. This might lead to increased treatment efficacy with the potential of omitting chemotherapy in these patients. The aim of the randomized multicenter phase III DETECT V trial was to analyze the efficacy of chemotherapy free and CDK4/6 inhibitor containing treatment strategies compared to current standard treatment. Methods: Between 09/2015 and 11/2022, 271 patients with HER2+ and HR+ MBC in the 1st-3rd line setting were randomized 1:1 to receive trastuzumab and pertuzumab combined with either endocrine therapy or chemotherapy followed by maintenance therapy with dual HER2 targeted and endocrine therapy. Chemotherapy and the endocrine agents could be chosen from a variety of available regimens according to physicians’ choice. In January 2019, the protocol was amended with the addition of the CDK4/6 inhibitor ribociclib to both treatment arms. The primary objective of DETECT V was to compare tolerability between the treatment arms, and secondary objectives comprised the comparison of overall survival (OS), progression-free survival (PFS) and safety, as well as the evaluation of the effect of adding ribociclib to both treatment arms. Here we report results of the final efficacy analyses as based on the modified ITT set of 262 patients (9 patients did not receive any study treatment and were excluded). Of these, 120 patients were recruited before the addition of ribociclib (59 and 61 patients in the chemotherapy-free and chemotherapy-containing treatment arm, respectively), and 142 patients were recruited after the addition of ribociclib (73 and 69 patients in the chemotherapy-free and chemotherapy-containing treatment arm, respectively). Results: Median patient age was 60 years, 202 (77.1%) of patients were in the first line setting and 137 (52.3%) patients had a metastasis-free interval (from primary diagnosis) exceeding 12 months. The overall comparison between all patients receiving chemotherapy-free and chemotherapy-containing treatment showed no significant difference with regard to OS and PFS (median OS not reached vs 46.1 months, HR 0.98, 95% CI 0.60 - 1.59, p = 0.93; median PFS 19.5 vs 23.0 months, HR 1.15, 95% CI 0.82 - 1.62, p = 0.42). However, both OS and PFS were significantly improved by the (non-randomized) addition of ribociclib (OS: median OS not reached vs 46.1 months, HR 0.43, 95% CI 0.26 - 0.72, p = 0.001; PFS: median PFS 29.7 vs 15.6 months, HR 0.48, 95% CI 0.34 - 0.67, p < 0.001). A separate analysis for the two treatment arms showed that the addition of ribociclib to chemotherapy-containing treatment significantly improved both OS (median OS not reached vs 38.7 months, HR 0.30, 95% CI 0.14 - 0.64, p = 0.002) and PFS (median PFS 33.1 vs 15.4 months, HR 0.35, 95% CI 0.21 - 0.59, p < 0.001), while the addition of ribociclib to chemotherapy-free treatment significantly improved PFS (median PFS 27.2 vs 15.6 months, HR 0.61, 95% CI 0.38 - 0.98, p = 0.040) but not OS (median OS not reached in both groups, HR 0.60, 95% CI 0.30 - 1.23, p = 0.163). An exploratory cross-cohort comparison revealed significantly improved outcome for patients receiving chemotherapy-free treatment plus ribociclib vs chemotherapy-containing treatment without ribociclib (OS: median OS not reached vs 38.7 months, HR 0.48, 95% CI 0.24 - 0.94, p = 0.033; PFS: median PFS 27.2 vs 15.4 months, HR 0.53, 95% CI 0.33 - 0.85, p = 0.008). Conclusion: Our results suggest that chemotherapy-free treatment for patients with HER2+ and HR+ MBC may be a valuable and effective treatment alternative, and may improve survival with the addition of ribociclib. Citation Format: W. Janni, T. Fehm, V. Müller, J. Blohmer, A. De Gregorio, T. Decker, A. Hartkopf, N. Ditsch, M. Schmidt, P. Wimberger, T. Engler, M. Banys-Paluchowski, P. A. Fasching, B. Rack, A. Schneeweiss, K. Pantel, T. W. Friedl, F. Schochter, J. Huober. Efficacy Analysis of the Randomized Phase III DETECT V trial: Treatment De-escalation by Omission of Chemotherapy and the Effect of Adding Ribociclib in HER2-positive and Hormone-receptor Positive Metastatic Breast Cancer [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 RF4-02.

Daylight photodynamic therapy is currently the preferred treatment for actinic keratosis due to its greater effectiveness and a lower level of pain compared to conventional photodynamic therapy. To enhance the effectiveness of the therapy, especially for hyperkeratotic forms, various pre-treatments are currently available, primarily fractional laser therapy. Until now, there have been few studies investigating skin physiology after photodynamic therapy and fractional laser treatment. The aim of the study was to investigate the skin physiological changes in daylight photodynamic therapy with and without fractional laser pre-treatment. Thirty patients with actinic keratoses were recruited at the Clinic for Dermatology, SLK Clinics Heilbronn, Germany. On the ventral right or left forearm of the patients, four fields of 3 x 3 cm each were randomly assigned to: daylight, fractional laser with daylight, daylight photodynamic therapy with 10% 5-aminolevulinic acid hydrochloride gel, and daylight photodynamic therapy with fractional laser with 10% 5-aminolevulinic acid hydrochloride gel. Redness, corneometry, and transepidermal water loss were measured before treatment, 30 minutes, 24 hours, seven days and 14 days after treatment. Compared to the effects of daylight photodynamic therapy alone, daylight photodynamic therapy with fractional laser caused more pronounced skin changes, with the increase persisting for up to 24 hours for transepidermal water loss values and up to 14 days for skin redness and dryness. Additional fractional laser was shown to intensify inflammatory processes and damage the skin barrier. This enhanced biological effect could also lead to an increased clinical effect on actinic keratoses.

BackgroundComputed tomography with fistulography (CTF) using contrast material (CM) injected into a fistula is commonly used to visualize fistulous tracts (FT) in chronic osteomyelitis or chronic wounds. Typically, a CT scan is done twice: first without CM to identify sequestrum, followed by using CM to visualize the FT.PurposeTo develop a streamlined and effective CTF method that reduces patient radiation exposure and lowers examination costs.Material and MethodsThe method employs hydrogen peroxide (H2O2) as a contrast agent. When H2O2 enters the FT, it breaks down into water and oxygen, spreading under low pressure. Since gas has a significantly lower radiopacity than iodinated contrast agents, gas-filled fistulas appear black on the CT monitor, while CM, foreign bodies, and bones appear white. This technique has been used in over 200 patients for the lower and uppser extremities, pelvis, spine, and chest.ResultsThe images enabled a simultaneous investigation of the spatial relationship between the FT and sequestrum, irrespective of the body segment examined. Only a single scan was necessary. No complications or discomfort were reported by the patients.ConclusionThis method enhanced the topographic diagnosis of FT and the spatial positioning of sequestrum or foreign bodies, halving patient radiation exposure. It eliminates the need for expensive iodinated contrast agents and their associated complications, significantly reducing examination costs and time.

e16548 Background: Patients with terminal renal failure (GFR <30 ml/min or dialysis), poor performance status (ECOG ≥2), and/or age ≥80 are often excluded or underrepresented in pivotal clinical trials evaluating enfortumab vedotin and pembrolizumab (EV/P) as first-line (1L) treatment in metastatic urothelial carcinoma (mUC). Consequently, data on safety and efficacy in these populations are limited. This study evaluates EV/P outcomes in this high-risk group. Methods: This multicenter, real-world, retrospective study included mUC patients receiving EV/P as 1L treatment who were underrepresented (age ≥ 80) or ineligible for the EV-302 trial due to GFR <30 ml/min, ECOG ≥2. Endpoints included overall and progression free survival (OS, PFS), objective response rate (ORR), and treatment-related adverse events (AE). Descriptive and survival analyses evaluated safety and efficacy in frail patients. Results: A total of 116 patients from 18 German tertiary care centers were treated between May 2022 and December 2024. The median age was 79 years (IQR 68–83), with 20.7% having a GFR <30 ml/min, 44.8% presenting with ECOG ≥2, and 49.1% aged ≥80. The median age-adjusted Charlson Comorbidity Index was 6 (IQR 4–8), highlighting the high burden of comorbidities in this population. The ORR was 54.1%, including an 8.1% complete response rate. The mPFS was 7.5 months (95% CI 5.9–NR), and the mOS was not reached. Any-grade AEs were reported in 72.2% of patients, with ≥grade 3 AEs in 31.3%. The most common treatment-related AEs were peripheral neuropathy (33.0%) and skin toxicity (23.3%). Among patients aged ≥80, 39% required dose reductions, compared to 31% in the overall cohort, occurring after a median of 68 days (IQR 42–137). Of all patients, 18.1% discontinued treatment due to progressive disease, with only 31.3% of them receiving subsequent anti-cancer therapy. In contrary a total of 26.7% of patients permanently discontinued EV/P due to toxicity or non-specified reasons, with a median treatment duration of 89 days (IQR 40–180). Conclusions: This retrospective real-world analysis suggests that EV/P demonstrates promising oncological efficacy, even in highly frail patients, including those with a GFR <30 ml/min, ECOG ≥2, or aged ≥80 years. However, frequent discontinuations in absence of disease progression underscore the need for prospective studies to evaluate more tolerable regimens and treatment interruptions strategies.

The VA ECMO Registry of Germany (VERGE, http://va-ecmo-register.de/ ) is a prospective, multicenter, investigator-driven registry of Venoarterial Extracorporeal Membrane Oxygenation (VA ECMO) all-comers, free from industrial support. VERGE is Germany's first multicenter registry to systematically gather and analyze data from various centers on the clinical use of VA ECMO. This first report compromises data from 581 VA ECMO patients from 2022. Median age was 60years, hospital survival was 42% and 25% were female. The leading indication for VA ECMO was extracorporeal cardiopulmonary resuscitation (ECPR) followed by VA ECMO in shock (48.9 and 34.9%, respectively). Hospital survival of ECPR was significantly worse compared to shock (28 and 55%, respectively, p < 0.001). Age, pH, and lactate before cannulation all significantly correlated independently with hospital survival (p < 0.001). In VERGE, no patients with pH below 6.7 or lactate above 25mmol/l survived.

ABSTRACTBackgroundOver the past years, some studies in amyotrophic lateral sclerosis (ALS) have provided heterogeneous findings regarding demographic and clinical data as well as the impact of various prognostic factors. It is well known that these inconsistencies might be caused by a selection bias in hospital‐based data sets. In this study, we sought to further characterize this selection bias.MethodsWe compared hospital‐based data from the ALS center at Ulm University (UC; n = 3833; 1997–2021) with the population‐based ALS registry Swabia (SR; n = 852; 2010–2020).ResultsPatients from UC were younger (age of onset 60.9 [IQR 52.4–68.9] vs. 65.0 [57.0–72.7]), had a higher share of males (60.5% vs. 56.3%), a longer diagnostic delay (10.5 [IQR 6.4–18.4] months vs. 6.9 [IQR 3.4–12.1] months), a higher prevalence of the “definite” category according to El Escorial diagnostic criteria (60.9% vs. 11.2%), a higher share of familial cases (12.9% vs. 6.3%), a slower progression rate (points of ALS functional rating scale revised lost per month −0.54 [IQR −1.02 to −0.28] vs. −0.79 [IQR −1.47 to −0.43]), and (among all deceased patients) a higher share of percutaneous endoscopic gastrostomy (26.7% vs. 17.7%) and non‐invasive ventilation (34.3% vs. 25.3%).ConclusionsThe observed differences likely indicate a selection bias in hospital‐based data, which may be attributed, among others, to the willingness to travel large distances to a specialized center, the desire to participate in clinical studies, and the attitude toward life‐prolonging measures. These differences must be considered when interpreting and generalizing study results from hospital‐based populations.

PurposeCurrently, the different types of ependymal neoplasm (EPN) are defined by anatomical localization and genetics. This retrospective multicenter study aimed to analyze the imaging patterns of both local and distant recurrences in supratentorial (ST) and posterior fossa (PF) EPN.MethodsWe exclusively evaluated patients with recurrent EPN. To form the basis for follow-up evaluations the imaging characteristics for ST-EPN and PF-EPN were assessed and compared to each other. Follow-up assessments included the idenTIFFication of local recurrent tumors, leptomeningeal dissemination, secondary intraparenchymal lesions, and extraneural metastases. MR-signal characteristics of local recurrent tumors were compared to the primary tumor.ResultsThe imaging series included 73 patients (median age at diagnosis 4.6 years; 56 PF-EPN). Recurrences were observed at up to five time points, with a total of 145 recurrence events documented. At first recurrence most PF-EPN recurred locally (29/56), while ST-EPN relapsed by intracranial dissemination (9/17). Local recurrent tumor grew fast and differed in up to one-fifth from the primary (13.2% lower T2-signal, 14.6% brighter T1-signal, 19% less contrast-enhancement). Leptomeningeal dissemination in ST-EPN is mainly restricted to intracranial (90.5%) while PF-EPN more frequently present with spinal spread (45.7%). Transient post-radiogenic lesions (n = 2) and secondary malignancies (n = 2) were rare. Extraneural metastases (n = 3) were found mainly near the surgical access.ConclusionRecurrences can occur multiple times in EPN patients, and the recurrence patterns differ between ST-EPN and PF-EPN. Imaging characteristics of local recurrences can differ from the primary tumor which is crucial for accurate diagnosis and treatment planning.