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Christine Brunner,1 Daniel Egle,1 Magdalena Ritter,1 Ricarda Kofler,1 Johannes M Giesinger,2 Lisa Schneitter,1 Monika Sztankay,2 Miriam Emmelheinz,1 Samira Abdel Azim,1 Verena Wieser,1 Anne Oberguggenberger2 1Department of Gynecology and Obstetrics, Medical University of Innsbruck, Innsbruck, Austria; 2Department of Psychiatry, Psychotherapy, Psychosomatics and Medical Psychology, Psychiatry II, Medical University of Innsbruck, Innsbruck, AustriaCorrespondence: Christine Brunner, Department of Gynecology and Obstetrics, Medical University of Innsbruck, Anichstraße 35, Innsbruck, 6020, Austria, Tel +43 512 504 81194, Email c.brunner@tirol-kliniken.atPurpose: Alopecia has been reported a distressing side-effect of chemotherapy for breast cancer patients (BCP) that is highly relevant for quality of life during treatment. For the prevention of chemotherapy-induced alopecia, scalp cooling (SC) has been reported to be an effective and safe intervention. However, data on the patient’s perspective on effectiveness and applicability of SC in a clinical routine setting are scarce. In this comparative study, we aimed at a longitudinal assessment of patient-reported outcome (PRO) data on the effect of SC on alopecia and its effect on symptoms and functional health when applied in clinical routine in BCP receiving taxane or anthracycline-based chemotherapy.Patients and Methods: Study participants were allocated either to the intervention group receiving SC or to the control group based on patient preference (non-randomized study). All patients completed PRO-measures on hair preservation (EORTC Item Library items on hair loss), symptom and functional health measures (EORTC QLQ-C30 and -BR23) and the Body Image Scale (BIS). Outcomes were assessed at chemotherapy start (baseline), mid-chemotherapy, last chemotherapy cycle, 3 months follow-up and 6– 9 months follow-up.Results: Overall, we included 113 patients: 75 patients underwent SC (mean age = 51.3 years, 52.7% premenopausal); 38 patients standard care (mean age = 55.6 years, 39.5% premenopausal). A total of 53 patients (70.7%) discontinued SC, with 39 patients (73.5%) stating alopecia as the primary reason. On average, BCP stayed on treatment with the cooling cap for 40.2% of the duration of their chemotherapy (SD 25.3%). In an intention-to-treat analysis, we found no difference between the SC group and the control group with regard to their patient-reported hair loss (p=0.831) across the observation period, overall QOL (p=0.627), emotional functioning (p=0.737), social functioning (p=0.635) and body image (p=0.463) did not differ between groups.Conclusion: We found a high rate of SC-decliners and no beneficial effects of SC for patient-reported hair loss, symptoms and functional health. The efficacy and tolerability of SC applied in a clinical routine setting hence appeared to be limited. The further determination and up-front definition of criteria prognostic for effectiveness of SC may be helpful to identify patient subgroups that may experience a treatment benefit.Keywords: cooling cap, self-report, alopecia, chemotherapy

Purpose: Medication-related osteonecrosis of the jaw (MRONJ) is one of the most important toxicities of antiresorptive therapy, which is standard practice for patients with breast cancer and bone metastases. However, the population-based incidence of MRONJ is not well established. We therefore performed a retrospective multicenter study to assess the incidence for a whole Austrian federal state (Tyrol)., Materials and Methods: This retrospective multicenter study was conducted between 2000 and 2020 at all nine breast centers across Tyrol, Austria. Using the cancer registry, the total Tyrolean population was screened for all patients with breast cancer. All patients with breast cancer and bone metastases receiving antiresorptive therapy were finally included in the study., Results: From 8,860 patients initially screened, 639 individuals were eligible and included in our study. Patients received antiresorptive therapy once per month without de-escalation of therapy. MRONJ was diagnosed in 56 (8.8%, 95% CI, 6.6 to 11.0) patients. The incidence of MRONJ was 11.6% (95% CI, 8.0 to 15.3) in individuals treated with denosumab only, 2.8% (95% CI, 0.7 to 4.8) in those treated with bisphosphonates only, and 16.3% (95% CI, 8.8 to 23.9) in the group receiving bisphosphonates followed by denosumab. Individuals developed MRONJ significantly earlier when treated with denosumab. Time to MRONJ after treatment initiation was 4.6 years for individuals treated with denosumab only, 5.1 years for individuals treated with bisphosphonates only, and 8.4 years for individuals treated with both consecutively., Conclusion: MRONJ incidence in breast cancer patients with bone metastases was found to be considerably higher, especially for patients receiving denosumab, when compared with available data in the literature. Additionally, patients treated with denosumab developed MRONJ significantly earlier.

Objectives: Neurotoxic effects causing peripheral nerve damage have been reported for several chemotherapy agents. There is no established and standardized method to assess the presence of chemotherapy-induced peripheral neuropathy (CIPN). We compared patient-reported CIPN symptoms to neurophysiological findings and neurological assessments in patients receiving taxane-based chemotherapy. Methods: Patients scheduled to receive taxane-based chemotherapy for the treatment of gynecologic cancer were included and prospectively followed for up to 9 months after chemotherapy discontinuation, between May 2020 and January 2023. Patient-reported symptoms, using the EORTC-QLQ-CIPN20 questionnaire, and nerve conduction studies (NCSs) were performed at baseline, halfway through the treatment cycle, at the end of the treatment, 3 months after treatment, and 6-9 months after treatment. Results: A total of 149 patients were included. Overall, 47.0% of patients reported symptoms compatible with CIPN at any of the follow-ups. Subjective symptoms did not correlate with nerve conduction studies. SNAP amplitudes at baseline were lower in patients who developed CIPN compared to the group without CIPN. Conclusions: The overall diagnostic accuracy of electrophysiological parameters as a marker for CIPN was low.

Objective: This study aimed to demonstrate the superiority of cryocompression over cryotherapy alone in the prevention of chemotherapy-induced peripheral neuropathy (CIPN) grade 2 or above., Methods: This prospective randomized study was conducted between May 2020 and January 2023 in Innsbruck. Eligible patients had a diagnosis of gynecological cancer and received a minimum of 3 cycles of taxane-based CT (neoadjuvant, adjuvant or palliative therapy). Patients were randomized 1:1 to receive either cryotherapy or cryocompression on their upper extremities during chemotherapy (CT). We performed temperature measurements, two QoL questionnaires and neurological tests during CT and at follow-up 3 and 6-9 months after the completion of CT. CIPN was assessed using the CTCAE score., Results: Of 200 patients recruited, both groups showed a lower prevalence of CIPN in this study compared to recent literature. In the group receiving cryotherapy, the prevalence of grade 1 CIPN was 30.1 %, and that of grade 2 CIPN or above was 13.7 %; in the group treated with cryocompression, the prevalence of grade 1 CIPN was 32.8 %, and that of grade 2 or above CIPN was 17.2 %. We found a significant reduction in temperature in the cryotherapy and cryocompression groups. Regarding the two QOL questionnaires as well as the neurological tests no significant differences were found between the two groups., Conclusion: Our study suggests that cryotherapy as well as cryocompression is a safe and effective way to cool patients' extremities to lower the prevalence of CIPN. Cryocompression was not more effective than cryotherapy alone in the prevention of CIPN., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Christine Brunner reports that financial support and administrative support were provided by Hilotherm (Germany) and a relationship with Hilotherm (Germany) that includes funding grants. Christine Brunner reports receiving consulting fees from Gilead Sciences and Novartis, honoraria for presentations from AMGEN, DaiichiSanyko, AstraZeneca, Gilead Sciences, SEAGEN, Pfizer and Novartis and support for attending meetings from DaiichiSanyko, AstraZeneca, and Novartis and participation on advisory board for Pfizer. Miriam Emmelheinz reports receiving support for attending meetings from Teva Ratiopharm and Sandoz. Daniel Egle reports receiving consulting fees from AstraZeneca, Daiichi-Sankyo, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz and Seagen and honoraria for presentations from Amgen, AstraZeneca, Daiichi-Sankyo, Gilead, Lilly, MSD, Novartis, Pfizer, Pierre-Fabre, Roche, Sandoz and Seagen and support for attending meetings from DaiichiSanyko, Gilead, Pfizer and AstraZeneca. Katharina Leitner reports receiving support for attending meetings from Gilead, GSK, Eisai and Roche. Verena Weiser reports receiving honoraria for presentations from Roche and Novartis and support for attending meetings from Roche. Christian Marth reports receiving consulting fees from Amgen, AstraZeneca; GlaxoSmithKline, MSD, Novartis, PharmaMar, Roche and Seagen and honoraria for presentations from Amgen, AstraZeneca, GlaxoSmithKline, MSD, Novartis, PharmaMar, Roche and Seagen and support for attending meetings from AstraZeneca and Roche. All other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) provide the unique opportunity to study the very early development of the human heart. The aim of this study was to investigate the effect of calcium and beta-adrenergic stimulation on the contractile properties of early hESC-CMs. Beating clusters containing hESC-CMs were co-cultured in vitro with noncontractile slices of neonatal murine ventricles. After 5-7 days, when beating clusters had integrated morphologically into the damaged tissue, isometric force measurements were performed during spontaneous beating as well as during electrical field stimulation. Spontaneous beating stopped when extracellular calcium ([Ca²⁺](ec)) was removed or after administration of the Ca²⁺ channel blocker nifedipine. During field stimulation at a constant rate, the developed force increased with incremental concentrations of [Ca²⁺](ec). During spontaneous beating, rising [Ca²⁺](ec) increased beating rate and developed force up to a [Ca²⁺](ec) of 2.5 mM. When [Ca²⁺](ec) was increased further, spontaneous beating rate decreased, whereas the developed force continued to increase. The beta-adrenergic agonist isoproterenol induced a dose-dependent increase of the frequency of spontaneous beating; however, it did not significantly change the developed force during spontaneous contractions or during electrical stimulation at a constant rate. Force developed by early hESC-CMs depends on [Ca²⁺](ec) and on the L-type Ca²⁺ channel. The lack of an inotropic reaction despite a pronounced chronotropic response after beta-adrenergic stimulation most likely indicates immaturity of the sarcoplasmic reticulum. For cell-replacement strategies, further maturation of cardiac cells has to be achieved either in vitro before or in vivo after transplantation.