Assessing circadian rhythms and chemotherapy safety in remote patients with pancreatic ductal adenocarcinoma (PDAC) using a multidimensional digital platform (MultiDom, NCT04263948).

Abstract

1650 Background: The disruption of circadian clocks is associated with reduced survival and treatment tolerability in cancer patients (pts). Here, real-time analyses of telemonitored circadian rhythms and electronic Pt-Reported Outcome (ePRO) are integrated within a multidimensional telemonitoring-telecare digital platform that triggers proactive telecare toward improved quality of life (QoL) and treatment safety. Methods: The multicentre, interventional, prospective, longitudinal, single-arm study recruited pts receiving mFOLFIRINOX chemotherapy (CT) q2-weeks for pancreatic ductal adenocarcinoma (PDAC). Early warning signals of circadian disruption, body weight loss, and ePROs severity are extracted from real time analysis and graphical displays of (i) continuously telemonitored rest-activity and chest surface temperature (chestemp) rhythms using a chest sensor, and (ii) daily body weight (e-balance), and (iii) daily self-rating of 23 symptoms using a GPRS tablet (MD Anderson Symptoms Inventory, MDASI). Pts participate for 1 week before (baseline) and 6 weeks after 1 st CT course. Circadian disruption is defined by an (I < O) value < 96%. (I < O) is the % accelerations per min In-Bed that are below median accelerations per min Out-of-Bed for 3 days; (I < O) range in controls, 97-100%). Automatic alerts are sent via internet for decision of proactive intervention by the oncology team, in case of circadian disruption, chestemp increase by 1.5°C, weight loss > 5%, or MDASI symptom ≥ 7. Results: From 6/2021 to 7/2024, 58 pts with advanced PDAC were selected (male, 52%), median age, 58 y.o. (range, 33-82); WHO performance status (PS) 0/1/2, 36%/53%/10% of the pts; metastatic sites 0/1/ > 2, 38%/24%/8%; liver metastases, 50%). Early PDAC-related complications prevented platform use in 5 pts. The platform was used by 53 pts during a median of 45.5 days (IQR, 38-50], with > 85% compliance. At baseline, large between-pts differences in circadian rhythms were found for both rest-activity I < O (median [IQR]), 98.4 accelerations/min [95.8-99.6]); range, 75 to 100), and chestemp circadian amplitude (median, 1.1°C [IQR, 0.7-1.4], range, 0.3°C to 2.7°C). Baseline circadian disruption was larger in male pts (56% vs 31%; p = 0.07) and in those with PS 1-2 (47% vs 14%; p = 0.02). Consistently, median chestemp circadian amplitude was less in males compared to females (0.8°C vs 1.3°C, p < 0.01) and in pts with PS = 1-2 compared to PS = 0 (0.8°C vs 1.3°C; p < 0.01). Maximum toxicities of CT were circadian disruption (100% of the pts), body weight loss > 5% (59%), and MDASI symptom ≥7 (46%), without any influence of baseline pt characteristics. Conclusions: The use of this multidimensional digital platform combining circadian and other physiology metrics with ePROs was feasible and accepted by the pts. Its implementation seemed to be clinically relevant toward improving the care of remote pts at risk of adverse events. Clinical trial information : 04263948.