Pressurized Intraperitoneal Aerosol Chemotherapy-Related Clinical Trials in the Treatment of Peritoneal Metastases.

INTRODUCTION: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a treatment option for patients with peritoneal metastases. We evaluated the current status of ongoing prospective clinical trials investigating PIPAC to provide an overview and predict trends in this field. METHODS: All 367,494 records of clinical trials registered at ClinicalTrials.gov were searched for trials dealing with PIPAC. Active or unpublished trials were further analyzed. RESULTS: In total, 22 clinical trials were identified and selected for further analyses. Most trials had a single-arm design and were phase I or II. No phase III trials were registered. Academic centers were recorded as primary sponsors in the majority of trials (63.6%). Every year, between 2 and 5 new trials were initiated. In 17 trials (81.8%), PIPAC was used in a palliative setting only, 2 trials performed PIPAC in a neoadjuvant setting, and 2 trials performed PIPAC in an adjuvant setting. Six different drugs (doxorubicin, cisplatin, oxaliplatin, nab-paclitaxel, 5-fluorouracil, and docetaxel) were used in these clinical trials. Most trials investigated the efficacy (n = 15) or safety (n = 7) of PIPAC therapies. CONCLUSIONS: The results of ongoing clinical trials will bring specific information on indications for PIPAC as well as the impact of PIPAC on quality of life and overall survival.

Current Research and Development in Hyperthermic Intraperitoneal Chemotherapy (HIPEC)-A Cross-Sectional Analysis of Clinical Trials Registered on ClinicalTrials.gov.

INTRODUCTION: Over the past two decades, cytoreductive surgery and HIPEC has improved outcomes for selected patients with peritoneal metastasis from various origins. This is a cross-sectional study with descriptive analyses of HIPEC trials registered on ClinicalTrials.gov. This study aimed to characterize clinical trials on HIPEC registered on ClinicalTrials.gov with the primary objective of identifying a trial focus and to examine whether trial results were published. METHODS: The search included trials registered from 1 January 2001 to 14 March 2022. We examined the associations of exposure variables and other trial features with two primary outcomes: therapeutic focus and results reporting. RESULTS: In total, 234 clinical trials were identified; 26 (11%) were already published, and 15 (6%) trials have reported their results but have not been published as full papers. Among ongoing nonpublished trials, 81 (39%) were randomized, 30 (14%) were blinded, n = 39 (20%) were later phase trials (i.e., phases 3 and 4), n = 152 (73%) were from a single institution, and 91 (44%) had parallel groups. Most of the trials were recruiting at the time of this analysis (75, 36%), and 39 (20%) were completed but had yet to publish results. In total, 68% of the trials focused on treatment strategies, and 53% investigated the oncological outcome. The most studied neoplasms for HIPEC trials were peritoneally metastasized colorectal cancer (32%), gastric cancer (29%), and ovarian cancer (26%). Twenty different drugs were analyzed in these clinical trials. CONCLUSIONS: Many study results are awaited from ongoing HIPEC trials. Most HIPEC trials focused on gastric, colorectal, or ovarian cancer. Many clinical trials were identified involving multiple entities and chemotherapeutic agents.

An innovative lung model for multiple breath washout testing in health and disease.

BACKGROUND: Multiple breath washout (MBW) is a lung function test that identifies the degree of ventilation inhomogeneity (VI) in the lungs. In vitro validation of MBW devices is recommended. So far, plastic lung models for MBW validation ignored variable degrees of VI. Our primary aim was to create a plastic lung model applicable for physiological lung volumes and variable VI. METHODS: A plastic box divided in two chambers was filled with water and ventilated in various lung volumes and respiratory rates. A ventilator was used for efficient gas distribution (model with low VI). An additional divider was inserted to create a model with high VI. The model was connected to commercial MBW devices and measurements were performed using different tracer gases and conditions. Primary outcome was the precision of generated functional residual capacity (FRC) and the ability to generate variable VI. The latter was estimated by lung clearance index (LCI) and expiratory phase III slopes (SIII). LCI was also compared to a mathematical model. FINDINGS: The intra-test variability for FRC was minimal, mean(SD) coefficient of variation 0.96(0.63)%, using different tracer gases under different conditions. Compared to the model with low VI, in the model with high VI LCI and washout SIII were significantly increased. LCI compared well to the mathematical model. INTERPRETATION: This novel lung model shows excellent precision in lung volumes and VI estimates independent of tracer gases and conditions. The model can mimic the lungs of patients with uneven gas distribution.

Comparison of different analysis algorithms to calculate multiple-breath washout outcomes.

Lung clearance index (LCI) is the main outcome of the multiple-breath washout (MBW) test. Current recommendations for LCI acquisition are based on low-grade evidence. The aim of this study was to challenge those recommendations using alternative methods for LCI analysis. Nitrogen MBW measurements from school-aged children, 20 healthy controls, 20 with cystic fibrosis (CF) and 17 with primary ciliary dyskinesia (PCD), were analysed using 1) current algorithms (standard), 2) three alternative algorithms to detect with higher precision the end of MBW testing and 3) two alternative algorithms to determine exhaled tracer gas concentrations. LCI values, intra-test repeatability, and ability to discriminate between health and lung disease were compared between these methods. The analysis methods strongly influenced LCI (mean±sd overall differences (%) between standard and alternative analysis methods: -4.9±5.7%; range: -66-19%), but did not improve intra-test variability. Discrimination between health and disease was comparable as areas under the receiver operator curves were not greater than that from standard analysis. This study supports current recommendations for LCI calculation in children. Alternative methods influence LCI estimates and hamper comparability between MBW setups. Alternative algorithms, whenever used, should be carefully reported.

Infant multiple breath washout using a new commercially available device: Ready to replace the previous setup?

INTRODUCTION: Multiple breath washout (MBW) is a sensitive test to measure lung volumes and ventilation inhomogeneity from infancy on. The commonly used setup for infant MBW, based on ultrasonic flowmeter, requires extensive signal processing, which may reduce robustness. A new setup may overcome some previous limitations but formal validation is lacking. AIM: We assessed the feasibility of infant MBW testing with the new setup and compared functional residual capacity (FRC) values of the old and the new setup in vivo and in vitro. METHODS: We performed MBW in four healthy infants and four infants with cystic fibrosis, as well as in a Plexiglas lung simulator using realistic lung volumes and breathing patterns, with the new (Exhalyzer D, Spiroware 3.2.0, Ecomedics) and the old setup (Exhalyzer D, WBreath 3.18.0, ndd) in random sequence. RESULTS: The technical feasibility of MBW with the new device-setup was 100%. Intra-subject variability in FRC was low in both setups, but differences in FRC between the setups were considerable (mean relative difference 39.7%, range 18.9; 65.7, P = 0.008). Corrections of software settings decreased FRC differences (14.0%, -6.4; 42.3, P = 0.08). Results were confirmed in vitro. CONCLUSION: MBW measurements with the new setup were feasible in infants. However, despite attempts to correct software settings, outcomes between setups were not interchangeable. Further work is needed before widespread application of the new setup can be recommended.