Chlormethin-Gel-basierte komplette Remission einer CD30-positiven Mycosis fungoides-Plaque

ZusammenfassungChlormethin-Gel ist seit Mai 2019 als Lokaltherapeutikum bei Erwachsenen für kutane T-Zell-Lymphome vom Typ Mycosis fungoides (MF) zugelassen. Die topische Anwendung erfolgt 1-mal täglich. Im Rahmen der Zulassungsstudie kam es nach einer mindestens 6-monatigen Behandlung mit Chlormethin-Gel bei 76,7 % der Patienten (69 von 90) zu einer ≥ 50 %-igen Verbesserung der klinischen Befunde, gemessen anhand der CAILS-Skala (Composite Assessment of Index Lesion Serverity). Eine komplette Remission wurde bei 19 % (17 von 90) der Patienten beschrieben. Etwas mehr als die Hälfte der behandelten Patienten zeigte lokale Nebenwirkungen mit Hautirritationen, Hautrötungen und auch Hautinfektionen. Weitere mögliche Hautreaktionen sind Pruritus, Blasenbildung und Geschwüre.Im Folgenden wird von einer Patientin mit einer bekannten CD30+-Mycosis fungoides im Stadium IIB (ISCL/EORTC 2007) berichtet. Eine unter verschiedenen Systemtherapien (Bexaroten, Bade-PUVA, Brentuximab Vedotin) immer wieder rezidivierende, ca. handtellergroße Plaque an der Flanke links wurde mit Chlormethin-Gel behandelt.Aufgrund bereits bekannter, langsam progredienter Größenzunahme und wiederholt schmerzhafter Mazerationen dieses Herdes erfolgte auch mit Blick auf mögliche Nebenwirkungen von Chlormethin-Gel die Behandlung in Absprache mit der Patientin nur jeden zweiten Tag.Unter diesem Therapieregime zeigte sich, nach anfänglicher kurzzeitiger Hautreizung, bereits nach 3 Monaten eine komplette, histologisch gesicherte, aktuell 6 Monate anhaltende Remission der Läsion.Diese Kasuistik soll einen eindrucksvollen Therapieverlauf unter Chlormethin-Gel in reduzierter Dosierung und bei guter Verträglichkeit präsentieren.

Evolution in lesion index durability using the new third generation laser balloon catheter for pulmonary vein isolation – does the mechanical innovation mean also clinical innovation?

Background The new second- and third-generation endoscopic ablation systems (EAS 2 and EAS 3) have been launched in recent years. We aimed to assess the index lesion durability as well as gap localization using the multigenerational novel technologies in patients with recurrent atrial fibrillation (AF). Methods Consecutive patients who underwent the second ablation for recurrent AF following the initial pulmonary vein isolation (PVI) with EAS 2 or EAS 3 were investigated. The persistent durability of PVI and gap localization at the second procedure were analyzed using spiral mapping catheter and three-dimensional mapping system. Results A total of 34 patients (EAS3: N=13, 50 PVs, EAS2: N=21, 82 PVs) were enrolled. Repeat procedure was performed mean 11.9±9.3 months after the initial procedure. Persistent durable isolation of all four PVs was recorded in 6 (46.2%) patients in EAS3 and 4 (19.1%) patients in EAS2 (P=0.130). Ninety-one out of 132 (68.9%) PVs were persistently isolated with a higher rate in EAS3 (EAS3: 82.0% vs. EAS2: 61.0%, P=0.0113). A total of 45 gaps were recorded in 41 PVs, of which right superior PV (RSPV) was the predominantly common reconnected vein (15 gaps in 14 PVs) irrespective of generation difference (EAS 3: 4 gaps in 3 PVs and EAS 2: 12 gaps in 11 PVs). Anterior-segment of RSPV was the most common gap distribution (EAS 3: 2 gaps and EAS 2: 6 gaps). Logistic multivariate regression analysis revealed high-dose (≥8.5W) only ablation as an independent predictor of durable PVI (adjusted OR: 3.70, 95% CI [1.408 - 10.003], P=0.008) Conclusion The multigenerational technical innovation resulted in a higher index lesion durability in EAS3 guided PVI in patients with recurrent AF. The specific gap patterns frequent at RSPV, especially at the anterior-superior segment, and the feasibility of high-dose ablation were confirmed in successor EASs. FUNDunding Acknowledgement Type of funding sources: None.

Diffusion-weighted MR imaging in chronic non-bacterial osteitis: Proof-of-concept of the apparent diffusion coefficient as an outcome measure

Background The apparent diffusion coefficient (ADC), as determined by whole-body diffusion-weighted MRI, may be useful as an outcome measure for monitoring response to treatment in chronic non-bacterial osteitis. Purpose To test and demonstrate the feasibility of ADC-measurement methods for use as outcome measure in chronic non-bacterial osteitis. Materials and Methods Using data from a randomized pilot study, feasibility of change-score ADC between baseline and second MRI (ΔADC12) and third MRI (ΔADC13) as outcome measure was assessed in three settings: “whole-lesion,” “single-slice per lesion,” and “index-lesion per patient”. Bone marrow edema lesions were depicted on short tau inversion recovery sequence at baseline and copied to ADC maps at the three time-points. Correlations between the three settings were measured as were analysis of variances. Discriminant validity was assessed as inter- and intra-observer reproducibility and smallest detectable change. Results 12 subjects were enrolled, and MRI was performed at baseline and weeks 12 and 36. Pearson correlation was high ( r > 0.86; p ≤ 0.01) for ΔADC between single-slice—whole-lesion and whole-lesion—index-lesion and tended to be significant for single-slice—index-lesion settings ( p = 0.06). For ΔADC12 and ΔADC13, Bland–Altman plots showed small differences (0.02, 0.03) and narrow 95% limits-of-agreement (−0.13–0.09, −0.07–0.05 μm2/s) between whole-lesion and single-slice ROI settings. Inter-observer reproducibility measured by intra-class correlation coefficient was poor-to-fair (range: 0.09–0.31), whereas intra-observer reproducibility was good-to-excellent (range: 0.67–0.90). Smallest detectable changes were between 0.21–0.28 μm2/s. Conclusion ADC change-score as outcome measure was feasible, and the single-slice per lesion ROI setting performed almost equally to whole-lesion setting resulting in reduced assessment time.

Intra-therapeutic dosimetry of [177Lu]Lu-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer patients and correlation with treatment outcome

Introduction While [177Lu]Lu-PSMA radioligand therapy is currently only applied in end-stage metastatic castrate-resistant prostate cancer (mCRPC) patients, also low-volume hormone-sensitive metastatic prostate cancer (mHSPC) patients can benefit from it. However, there are toxicity concerns related to the sink effect in low-volume disease. This prospective study aims to determine the kinetics of [177Lu]Lu-PSMA in mHSPC patients, analyzing the doses to organs at risk (salivary glands, kidneys, liver, and bone marrow) and tumor lesions < 1 cm diameter. Methods Ten mHSPC patients underwent two cycles of [177Lu]Lu-PSMA therapy. Three-bed position SPECT/CT was performed at 5 time points after each therapy. Organ dosimetry and lesion dosimetry were performed using commercial software and a manual approach, respectively. Correlation between absorbed index lesion dose and treatment response (PSA drop of > 50% at the end of the study) was calculated and given as Spearman’s r and p-values. Results Kinetics of [177Lu]Lu-PSMA in mHSPC patients are comparable to those in mCRPC patients. Lesion absorbed dose was high (3.25 ± 3.19 Gy/GBq) compared to organ absorbed dose (salivary glands: 0.39 ± 0.17 Gy/GBq, kidneys: 0.49 ± 0.11 Gy/GBq, liver: 0.09 ± 0.01 Gy/GBq, bone marrow: 0.017 ± 0.008 Gy/GBq). A statistically significant correlation was found between treatment response and absorbed index lesion dose (p = 0.047). Conclusions We successfully performed small lesion dosimetry and showed that the tumor sink effect in mHSPC patients is of less concern than was expected. Tumor-to-organ ratio of absorbed dose was high and tumor uptake correlates with PSA response. Additional treatment cycles are legitimate in terms of organ toxicity and could lead to better tumor response.