The chemokine CXCL12 promotes glioblastoma (GBM) recurrence after radiotherapy (RT) by facilitating vasculogenesis. Here we report outcomes of the dose-escalation part of GLORIA (NCT04121455), a phase I/II trial combining RT and the CXCL12-neutralizing aptamer olaptesed pegol (NOX-A12; 200/400/600 mg per week) in patients with incompletely resected, newly-diagnosed GBM lacking MGMT methylation. The primary endpoint was safety, secondary endpoints included maximum tolerable dose (MTD), recommended phase II dose (RP2D), NOX-A12 plasma levels, topography of recurrence, tumor vascularization, neurologic assessment in neuro-oncology (NANO), quality of life (QOL), median progression-free survival (PFS), 6-months PFS and overall survival (OS). Treatment was safe with no dose-limiting toxicities or treatment-related deaths. The MTD has not been reached and, thus, 600 mg per week of NOX-A12 was established as RP2D for the ongoing expansion part of the trial. With increasing NOX-A12 dose levels, a corresponding increase of NOX-A12 plasma levels was observed. Of ten patients enrolled, nine showed radiographic responses, four reached partial remission. All but one patient (90%) showed at best response reduced perfusion values in terms of relative cerebral blood volume (rCBV). The median PFS was 174 (range 58-260) days, 6-month PFS was 40.0% and the median OS 389 (144-562) days. In a post-hoc exploratory analysis of tumor tissue, higher frequency of CXCL12⁺ endothelial and glioma cells was significantly associated with longer PFS under NOX-A12. Our data imply safety of NOX-A12 and its efficacy signal warrants further investigation.

Purpose: Radiation-induced skin injury represents one of the most common side effects in breast cancer patients receiving adjuvant whole-breast radiotherapy. Numerous systemic and topical treatments have been studied in the prevention and management of radiation-induced skin injury without providing sustainable treatment strategies. While superficial barrier-forming skin products such as dressings are the standard of care in wound care management, their utilization as preventive treatment approach in radiotherapy has barely attracted attention. Methods: In this prospective, intra-patient randomized study, Hydrofilm polyurethane film dressings were applied prophylactically to either the medial or lateral breast half of 62 patients with breast cancer undergoing adjuvant radiation therapy following breast conserving surgery. The breast half contralateral to the film dressing was concurrently treated with 5% urea lotion as control skin care. Maximum severity of radiation dermatitis was assessed using RTOG/EORTC toxicity scores, photospectrometric erythema measurements and patient-assessed modified RISRAS scale. Results: In the Hydrofilm compartments, mean maximum RTOG/EORTC radiation dermatitis severity grades were significantly reduced from 1.33 to 0.35 and photospectrometric measurements showed significantly reduced erythema severity, as compared to the control compartments, with an overall response rate of 89.3%. Hydrofilm completely prevented moist desquamation and significantly reduced patients’ subjective experience of itching and pain. Conclusion: The obtained results along with a favorable cost–benefit ratio and an easy and quick application suggest a prophylactic application of Hydrofilm in adjuvant radiotherapy of breast cancer patients to reduce or even prevent radiation dermatitis.

Radiation-induced skin injury represents the most frequent side effect in breast cancer patients undergoing whole-breast irradiation (WBI). Numerous clinical studies on systemic and topical treatments for radiation dermatitis have failed to provide sustainable treatment strategies. While protective skin products such as dressings are undoubtedly the standard of care in wound care management, their utilization as preventive treatment in radiotherapy has been somewhat neglected in recent years. In this prospective, intra-patient randomized observational study, Hydrofilm polyurethane films were prophylactically applied to either the medial or lateral breast-half of 74 patients with breast cancer undergoing hypofractionated whole-breast irradiation following breast-preserving surgery. Maximum radiation dermatitis severity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 toxicity scores, photospectrometric erythema and pigmentation measurements and patient-assessed modified Radiation-Induced Skin Reaction Assessment Scale (RISRAS) scale. Phantom studies revealed a clinically negligible dose build-up of less than 0.1% with Hydrofilm. Compared to the control compartments physician-assessed radiation dermatitis severity was reduced in the hydrofilm compartments (mean 0.54 vs. 1.34; p = < 0.001). Objective photospectrometric skin measurements showed decreased erythema (p = 0.0001) and hyperpigmentation (p = 0.002) underneath Hydrofilm. Hydrofilm also completely prevented moist desquamation, and significantly reduced patients’ treatment-related symptoms of itching, burning, pain, and limitations of day-to-day-activities. Significant beneficial effects were observed in terms of radiation dermatitis severity, erythema, hyperpigmentation as well as subjective treatment-related symptom experiences, while adverse reactions were rare and minor. Therefore, a prophylactic application of Hydrofilm polyurethane films can be suggested in hypofractionated WBI.

Background: Radiation-induced dermatitis (RID) is frequent in breast cancer patients undergoing radiotherapy (RT). Spectrophotometry (SP) is an objective and reliable tool for assessing RID severity. Despite intensive research efforts during the past decades, no sustainable prophylactic and treatment strategies have been found. Estimation of new and reevaluation of established risk factors leading to severe RID is therefore of major importance. Methods: 142 early breast cancer patients underwent whole-breast irradiation following breast-conserving surgery. RID was evaluated by physician-assessed Common Terminology Criteria of Adverse Events (CTCAE v4.03). Spectrophotometers provided additional semi quantification of RID using the L*a*b color-space. A total of 24 patient- and treatment-related parameters as well as subjective patient-assessed symptoms were analyzed. Results: Values for a*max strongly correlated with the assessment of RID severity by physicians. Breast volume, initial darker skin, boost administration, and treatment technique were identified as risk factors for severe RID. RID severity positively correlated with the patients’ perception of pain, burning, and reduction of everyday activities. Conclusions: Physician-assessed RID gradings correlate with objective SP skin measurements. Treatment technique and high breast volumes were identified as objective and significant predictors of RID. Our data provide a solid benchmark for future studies on RID with objective SP.