Study protocol for OptimalTTF-2: enhancing Tumor Treating Fields with skull remodeling surgery for first recurrence glioblastoma: a phase 2, multi-center, randomized, prospective, interventional trial.

BACKGROUND: OptimalTTF-2 is a randomized, comparative, multi-center, investigator-initiated, interventional study aiming to test skull remodeling surgery in combination with Tumor Treating Fields therapy (TTFields) and best physicians choice medical oncological therapy for first recurrence in glioblastoma patients. OptimalTTF-2 is a phase 2 trial initiated in November 2020. Skull remodeling surgery consists of five burrholes, each 15 mm in diameter, directly over the tumor resection cavity. Preclinical research indicates that this procedure enhances the effect of Tumor Treating Fields considerably. We recently concluded a phase 1 safety/feasibility trial that indicated improved overall survival and no additional toxicity. This phase 2 trial aims to validate the efficacy of the proposed intervention. METHODS: The trial is designed as a comparative, 1:1 randomized, minimax two-stage phase 2 with an expected 70 patients to a maximum sample size of 84 patients. After 12-months follow-up of the first 52 patients, an interim futility analysis will be performed. The two trial arms will consist of either a) TTFields therapy combined with best physicians choice oncological treatment (control arm) or b) skull remodeling surgery, TTFields therapy and best practice oncology (interventional arm). Major eligibility criteria include age ≥ 18 years, 1st recurrence of supratentorial glioblastoma, Karnofsky performance score ≥ 70, focal tumor, and lack of significant co-morbidity. Study design aims to detect a 20% increase in overall survival after 12 months (OS12), assuming OS12 = 40% in the control group and OS12 = 60% in the intervention group. Secondary endpoints include hazard rate ratio of overall survival and progression-free survival, objective tumor response rate, quality of life, KPS, steroid dose, and toxicity. Toxicity, objective tumor response rate, and QoL will be assessed every 3rd month. Endpoint data will be collected at the end of the trial, including the occurrence of suspected unexpected serious adverse reactions (SUSARs), unacceptable serious adverse events (SAEs), withdrawal of consent, or loss-to-follow-up. DISCUSSION: New treatment modalities are highly needed for first recurrence glioblastoma. Our proposed treatment modality of skull remodeling surgery, Tumor Treating Fields, and best practice medical oncological therapy may increase overall survival significantly. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0422399 , registered 13. January 2020.

Antibiotic treatment interruption of suspected lower respiratory tract infections based on a single procalcitonin measurement at hospital admission--a randomized trial.

Recent studies have suggested that procalcitonin (PCT) is a safe marker for the discrimination between bacterial and viral infection, and that PCT-guided treatment may lead to substantial reductions in antibiotic use. The present objective was to evaluate the effect of a single PCT measurement on antibiotic use in suspected lower respiratory tract infections (LRTIs) in a Danish hospital setting. In a randomized, controlled intervention study, 223 adult patients admitted to the hospital because of suspicion of LRTI were included with 210 patients available for analysis. Patients were randomized to either PCT-guided treatment or standard treatment. Antibiotic treatment duration in the PCT group was based on the serum PCT value at admission. The cut-off point for recommending antibiotic treatment was PCT > or =0.25 microg/L. Physicians could overrule treatment guidelines. The mean duration of hospital stay was 5.9 days in the PCT group vs. 6.7 days in the control group (p 0.22). The mean duration of antibiotic treatment during hospitalization in the PCT group was 5.1 days on average, as compared to 6.8 days in the control group (p 0.007). In a subgroup analysis of chronic obstructive pulmonary disease patients, the mean length of stay was reduced from 7.1 days in the control group to 4.8 days in the PCT group (p 0.009). It was concluded that the determination of a single PCT value at admission in patients with suspected LRTIs can lead to a reduction in the duration of antibiotic treatment by 25% without compromising outcome. No effect on the length of hospital stay was found.