Personalized frailty risk assessment in long-term survivors of colorectal cancer.
Authors: Forman Rebecca , Westvold Sarah , Long Jessica B. , Fan Jane , Hyslop Terry , Yasin Faiza , Conlin Kerry , Jacobson Sofia I , Silber Andrea , Wang Shi-Yi , Leapman Michael , Leeds Ira L , Cecchini Michael , Spees Lisa P. , Wheeler Stephanie B. , Gross Cary Philip , Oeffinger Kevin C. , Dinan Michaela Ann 
Published: January 2025

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Background:
Frailty, a pathologic form of aging, is associated with reduced quality of life and increased risk of death. Its incidence increases with age. Frailty is a concern for cancer survivors, especially since this population is surviving longer and increasing in size. There is a need to predict which patients are at risk of frailty to tailor preventative measures, particularly in early-stage colon and rectal cancer survivors, the largest group in gastrointestinal cancer survivors.
Methods:
This was a retrospective cohort study of individuals aged 66 and older in the SEER-Medicare linked database, diagnosed with stage I-III colon or rectal cancer between 2003-2012. Patients included in the study received definitive surgical treatment and survived for at least 5 years after diagnosis. Frailty was assessed using administrative claims codes with the Kim frailty index. Patients already frail at year 5 were excluded from the analysis. An increase in frailty score, indicating the onset of frailty or worsening to moderate or severe frailty, occurring within 5-10 years following cancer diagnosis was the primary outcome. Predictors of frailty were identified using restricted mean survival time (RMST) regression, with results less than 1 indicating a shorter time to frailty, and significant factors were used to develop a clinical prediction model and stratify patients into risk tertiles.
Results:
At 10 years or end of available follow-up, 58% of the patients had developed new onset or worsening frailty. There were no significant differences in RMST by patient race, sex, cancer stage and grade. Receipt of systemic therapy 4-5 years after diagnosis, having an ostomy present in years 4-5, advancing age, comorbidities, and living in an area with a greater proportion of residents below the federal poverty line were all associated with shorter time to frailty; the largest effects were seen with advancing age and comorbidities (Table). Our clinical prediction model incorporated age>85 and having multiple comorbidities for both cohorts and ostomy in years 4-5 for the colon cohort.
Conclusions:
Our population level analysis provided a clinical prediction model for frailty 5-10 years after cancer diagnosis in colon and rectal cancer survivors and may help inform long-term survivorship management.

RMST for selected variables.

Selected Variables
RMST for Colon Cohort (95% CI)
RMST for Rectal Cohort (95% CI)

Age 85-89 (ref: age 71-74)
0.76 (0.73, 0.79)
0.79 (0.74, 0.84)

Age 90+ (ref: age 71-74)
0.67 (0.64, 0.70)
0.74 (0.66, 0.82)

20-100% area-level poverty (ref: 0-<5%)
0.95 (0.92, 0.98)
0.96 (0.91, 1.02)

Receiving systemic therapy in years 4-5
0.89 (0.85, 0.92)
Not selected

Ostomy in years 4-5
0.80 (0.69, 0.92)
0.97 (0.92, 1.02)

Elixhauser Comorbidity Index (ECI) 1-2 (reference: ECI 0)
0.77 (0.75, 0.79)
0.79 (0.76, 0.82)

ECI 3 (ref: ECI 0)
0.60 (0.57, 0.64)
0.67 (0.59, 0.76)