Plasma extracellular vesicles in meningioma patients following radiotherapy as liquid biopsy- a prospective explorative biomarker study (ARO 2023-05/AG-NRO-07).

BACKGROUND: While surgical resection remains the primary treatment approach for symptomatic or growing meningiomas, radiotherapy represents an auspicious alternative in patients with meningiomas not safely amenable to surgery. Biopsies are often omitted in light of potential postoperative neurological deficits, resulting in a lack of histological grading and (molecular) risk stratification. In this prospective explorative biomarker study, extracellular vesicles in the bloodstream will be investigated in patients with macroscopic meningiomas to identify a biomarker for molecular risk stratification and disease monitoring. METHODS: In total, 60 patients with meningiomas and an indication of radiotherapy (RT) and macroscopic tumor on the planning MRI will be enrolled. Blood samples will be obtained before the start, during, and after radiotherapy, as well as during clinical follow-up every 6 months. Extracellular vesicles will be isolated from the blood samples, quantified and correlated with the clinical treatment response or progression. Further, nanopore sequencing-based DNA methylation profiles of plasma EV-DNA will be generated for methylation-based meningioma classification. DISCUSSION: This study will explore the dynamic of plasma EVs in meningioma patients under/after radiotherapy, with the objective of identifying potential biomarkers of (early) tumor progression. DNA methylation profiling of plasma EVs in meningioma patients may enable molecular risk stratification, facilitating a molecularly-guided target volume delineation and adjusted dose prescription during RT treatment planning.

Pelvic Irradiation for Node-Positive Prostate Cancer After Prostatectomy: Long-Term Results of the Prospective PLATIN-4 and PLATIN-5 Trials.

PURPOSE: After radical prostatectomy (RP), adjuvant or salvage radiation treatment in node-positive prostate cancer is offered to prevent systemic disease. Prospective long-term survival and toxicity data on patients with radiation for nodal disease are still scarce. This study evaluates safety and feasibility of salvage radiation therapy to the pelvic lymph nodes in node-positive prostate cancer after RP. METHODS AND MATERIALS: Between 2009 and 2018, 78 patients with lymph node recurrence after RP (PLATIN-4 trial) or after RP and prostate bed radiation therapy (PLATIN-5 trial) were treated with salvage pelvic lymph node radiation therapy with boost to the involved nodes as field abutment (PLATIN-5) and boost to the prostate bed (PLATIN-4). Androgen deprivation therapy was started 2 months before radiation and recommended for 24 months. The primary endpoint was safety and feasibility of the intensity modulated radiation therapy-image guided radiation therapy technique based on the rate of treatment discontinuations and incidence of Common Terminology Criteria for Adverse Events grade 3+ toxicity. Secondary endpoints were progression-free survival and overall survival. RESULTS: No treatment discontinuations were reported in either trial. Median overall survival was not reached in PLATIN-4 and was 117 months in PLATIN-5. Median progression-free survival was 66 months in PLATIN-4 and 39 months in PLATIN-5. Late grade 3+ genitourinary and gastrointestinal toxicities were observed in 4% of patients at 24 months of follow-up. CONCLUSIONS: Salvage radiation therapy to the prostate bed and pelvic lymphatic drainage combined with long-term androgen deprivation therapy is a curative treatment option for patients with node-positive prostate cancer after RP, with excellent in-field disease control. Pelvic lymph node radiation therapy as field abutment after prostate bed radiation therapy is feasible with long-term survival and no high-grade toxicity.

Oral Sequelae after Head and Neck Radiotherapy: RCT Comparing 3D-Printed Tissue Retraction Devices with Conventional Dental Splints.

OBJECTIVES: To evaluate oral sequelae after head and neck radiotherapy (RT) when using two different types of intraoral appliances. Thermoplastic dental splints (active control) protect against backscattered radiation from dental structures. Semi-individualized, 3D-printed tissue retraction devices (TRDs, study group) additionally spare healthy tissue from irradiation. MATERIALS AND METHODS: A total of 29 patients with head and neck cancer were enrolled in a randomized controlled pilot trial and allocated to receive TRDs (n = 15) or conventional splints (n = 14). Saliva quality and quantity (Saliva-Check, GC), taste perception (Taste strips, Burghart-Messtechnik), and oral disability (JFLS-8, OHIP-14, maximum mouth opening) were recorded before and 3 months after RT start. Radiotherapy target volume, modality, total dose, fractionation, and imaging guidance were case-dependent. To evaluate intra-group developments between baseline and follow-up, nonparametric Wilcoxon tests were performed. Mann-Whitney-U tests were applied for inter-group comparisons. RESULTS: At follow-up, taste perception was unimpaired (median difference in the total score; TRDs: 0, control: 0). No significant changes were found regarding oral disability. Saliva quantity (stimulated flow) was significantly reduced with conventional splints (median -4 mL, p = 0.016), while it decreased insignificantly with TRDs (median -2 mL, p = 0.07). Follow-up was attended by 9/15 study group participants (control 13/14). Inter-group comparisons showed no significant differences but a tendency towards a better outcome for disability and saliva quality in the intervention group. CONCLUSION: Due to the small cohort size and the heterogeneity of the sample, the results must be interpreted with reservation. Further research must confirm the positive trends of TRD application. Negative side-effects of TRD application seem improbable.