Objectives: To determine safety, feasibility, and preliminary activity of transtympanic injection of sodium thiosulfate (STS) against cisplatin-induced hearing loss (CIHL). DESIGN Randomized... Show moreObjectives: To determine safety, feasibility, and preliminary activity of transtympanic injection of sodium thiosulfate (STS) against cisplatin-induced hearing loss (CIHL). DESIGN Randomized controlled trial. SETTING Tertiary cancer hospital. PATIENTS Adults to be treated with high-dose cisplatin (>= 75 mg/m(2)). INTERVENTION Selected by randomization, 0.1 M STS gel on one side and placebo gel on the other side was transtympanically applied to the middle ear 3 hours before cisplatin administration. After amendment, the placebo ear was left untreated. Main Outcome Measure: Primary outcome was safety and feasibility. Secondary outcomes included pharmacokinetic analysis of systemic cisplatin and preliminary activity of STS. Clinically relevant CIHL was defined as a >= 10 dB threshold shift at pure-tone average 8-10-12.5 kHz (PTA(8-12.5)). Response to STS was defined as a threshold shift at PTA(8-12.5) in the STS-treated ear of >= 10 dB smaller than the untreated ear. Results: Twelve patients were treated. Average CIHL at PTA(8-12.5) was 12.7 dB in untreated ears and 8.8 dB SPL in STS-treated ears (p = 0.403). Four patients did not develop CIHL. Four out of eight patients with CIHL responded to STS: CIHL at PTA(8-12.5) in STS-treated ears was 18.4 dB less compared to untreated ears (p = 0.068). Grade 1 adverse events were reported. Pharmacokinetic results were available for 11 patients. Conclusion: Transtympanic application of STS was safe and feasible. Based on our pharmacokinetic analysis, we postulate that transtympanic STS does not interfere with the systemically available cisplatin. Our results provide a preliminary proof of concept for transtympanic application of STS in preventing CIHL and warrants further evaluation on a larger scale. Show less
Lansu, J.; Groenewegen, J.; Coevorden, F. van; Houdt, W. van; Akkooi, A.C.J. van; H. van boven; ... ; Haas, R.L. 2019
Aims: The purpose of the study was to investigate the time dependent dynamics of wound complications and local control after preoperative radiotherapy (RT) in Extremity Soft Tissue Sarcomas (ESTS)... Show moreAims: The purpose of the study was to investigate the time dependent dynamics of wound complications and local control after preoperative radiotherapy (RT) in Extremity Soft Tissue Sarcomas (ESTS).Patients & methods: In this retrospective cohort study, all patients treated for an extremity sarcoma with pre-operative radiotherapy followed by surgery were identified from a prospectively maintained database. A wound complication (WC) was defined as any local complication of the surgical area requiring intervention, hospital readmission or significant extension of the initial admission period.Results: A total of 191 preoperatively irradiated ESTS patients were included in this study. WC was seen in 31% of the patients (n=60). WC started after a median time of 25 days from surgery, with a median duration of 76 days. Adiposity, smoking and a lower extremity or superficial tumor localization were significantly correlated with an increased WC rate. Risk factors for a duration of WC >= 120 days are early development of WC (<= 21 days after surgery) and smoking. Local control rates after 1, 3 and 5 years were 99%, 93% and 93%, respectively.Conclusion: Approximately one-third of patients selected for preoperative RT develops a WC, typically in smoking, adipose patients with superficial tumor localizations in the lower extremity. Based upon the well-established superior long-term functional outcome, maintained excellent local control rates and the temporary nature of the WC issue, preoperative RT remains our preferred treatment. Although, in patients at high risk of WC, post-operative RT might be considered. (C) 2018 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Caliebe, J.; Broekman, S.; Boogaard, M.; Bosch, C.A.J.; Ruivenkamp, C.A.L.; Oostdijk, W.; ... ; Losekoot, M. 2012
