Associations of symptom burden with patient-reported outcomes (PROs) and clinical outcomes among early phase cancer clinical trial (EP-CT) participants.
Authors: Lam Anh B. , Lundquist Debra , Pelletier Andrea , Durbin Sienna , Petrillo Laura A , Jimenez Rachel , Turbini Victoria , Bame Viola , Lynch Kaitlyn , Boulanger Mary Catherine , Moore Cynthia , Yalala Vaishnavi , Ollila Nicholas , Malowitz Benjamin , McIntyre Casandra , Juric Dejan , Nipp Ryan David 
Published: September 2024

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Background:
Individuals with cancer often endure a substantial physical and psychological symptom burden. However, little is known about the baseline symptom burden of patients with cancer participating in EP-CTs or the associations of this symptom burden with other PROs and clinical outcomes.
Methods:
We prospectively enrolled adults with cancer participating in EP-CTs at Massachusetts General Hospital from 4/2021-1/2023. Participants completed baseline surveys prior to EP-CT initiation that assessed symptoms (Edmonton Symptom Assessment System [ESAS]), quality of life (QOL; Functional Assessment of Cancer Therapy-General), hope (Herth Hope Index), depression/anxiety symptoms (Patient Health Questionnaire-4 [PHQ-4]), and financial wellbeing (COST tool, higher scores indicate greater financial wellbeing). We used regression models to explore associations of baseline symptom burden with other PROs (QOL, hope, depression/anxiety, financial wellbeing) and clinical outcomes (time on trial, hospitalizations, overall survival).
Results:
Among 205 participants (median age=63.3 [range: 31.8-88.6], 57.1% female), the most common cancer types were gastrointestinal (34.6%), breast (20.0%), and head and neck (10.2%). Based on the ESAS, approximately half of participants reported moderate/severe fatigue (50.2%) and poor wellbeing (49.5%). Under half reported moderate/severe drowsiness (35.7%), pain (25.9%), lack of appetite (25.4%), shortness of breath (20.0%), anxiety (18.0%), depression (15.4%), and nausea (9.2%). Higher baseline ESAS total, physical, and psychological scores were associated with worse QOL, lower hope, greater PHQ-4 depression/anxiety symptoms, and worse financial wellbeing (see Table). Higher baseline ESAS scores were associated with decreased time on trial and worse overall survival (see Table).
Conclusions:
In this study of EP-CT participants, we found associations of baseline symptom burden with other important PROs and clinical outcomes. Specifically, higher baseline symptom burden was associated with decreased QOL, lower hope, increased depression/anxiety symptoms, and diminished financial wellbeing as well as greater risk for shorter time on trial and worse survival. Interventions seeking to enhance care delivery and outcomes for EP-CT participants should strive to address the symptom burden of this population.

Outcomes
ESAS Total
ESAS Physical
ESAS Psychological

PROs
Beta
P
Beta
P
Beta
P

QOL
-0.55

<0.001

-0.68

<0.001

-1.93

<0.001

Hope
-0.10

<0.001

-0.09

<0.001

-0.53

<0.001

PHQ-4 Depression/Anxiety
0.06

<0.001

0.06

<0.001

0.39

<0.001

Financial Wellbeing
-0.13

0.003

-0.16

0.009

-0.36

0.032

Clinical Outcomes
HR
P
HR
P
HR
P

Hospitalizations
1.01
0.066
1.02
0.059
1.03
0.290

Time on Trial
1.01
0.069
1.01
0.208
1.04

0.046

Overall Survival
1.02

<0.001

1.03

<0.001

1.04
0.088