Page 165 - Haematologica May 2022

RCT of geriatric consultation in blood cancers
There is strong evidence from observational studies that, in comparison with standard oncologic assessment, GA better identifies age-related vulnerabilities, guides the care of these vulnerabilities, influences treatment decisions, and predicts outcomes in older patients with cancer.9-14 Moreover, recent randomized controlled trials suggest that GA-guided interventions may reduce treatment toxicity, improve quality of life, and improve communication with patients and caregivers.15-17 Unfortunately, these trials include mainly older patients with solid tumors. To our knowledge, no similar trials in patients with blood cancers have been reported. We thus leveraged the embedded geri- atrics resources available in our outpatient blood cancer clinic to determine the impact of consultation with a geria- trician alongside standard oncologic care for patients aged 75 and older with hematologic malignancies.
Methods
Patients and study design
This randomized controlled trial enrolled patients from February 2015 to May 2018 (ClinicalTrials.gov identifier NCT02359838) (Online Supplementary File S1). Eligible patients included all patients aged 75 years and older who presented to Dana-Farber Cancer Institute (Boston, MA, USA) for initial consul- tation seeking management for newly diagnosed or previously diagnosed and treated lymphoma, leukemia, or multiple myelo- ma. Patients were ineligible if they were referred for consultation for stem cell transplantation or did not plan to continue their care at our institution. Eligible patients who consented to participate in the study underwent an in-person screening GA administered by a research assistant on the same day as their initial hematologic oncology consultation, as described previously.5 From this assess- ment, frailty status was derived using both the phenotypic and deficit-accumulation approaches - two of the most widely-studied approaches in aging research (see the protocol in Online Supplementary File S1 for further details regarding these approaches and their cut-off values that classified severity of frailty).18,19 In brief, the frailty phenotype uses five criteria to define a syndrome (slow gait, weakness [grip strength], self-reported exhaustion, low physical activity, and weight loss; average time to complete, 5-10 minutes). The deficit-accumulation method counts numerous aging-related health deficits across multiple domains from a GA to define frailty as the proportion of deficits present in an individual out of the total number of possible deficits measured (average time to complete, 15-20 minutes). We did not use a disease-specif- ic frailty score such as the International Myeloma Working Group score. Patients classified as pre-frail or frail by either approach were randomized to either standard oncologic care as they would normally receive at Dana-Farber or standard care plus embedded consultation provided by a geriatrician. All oncologists were blind- ed to the initial geriatric screening and frailty classification, pre- cluding an influence on initial treatment recommendations. Oncologists of patients in the intervention group may have become aware of patients’ frailty status later in the study after the patients had been assessed by the geriatrician.
Randomization was stratified by disease type to minimize potential imbalances in blood cancers and treatments. Randomization was first conducted on a 1:1 ratio but was switched to a 2:1 ratio (standard care: standard care plus geriatric consultation) to increase enrollment, which was initially limited due to difficulties in scheduling patients assigned to the interven- tion arm to one of the twice-weekly geriatric clinic sessions. The study was powered to detect a difference in 1-year overall survival
(the primary outcome) of 25% between study arms, hypothesiz- ing that the geriatric consultation arm would demonstrate this per- cent improvement in survival. This effect size was estimated based on prior observational data regarding survival rates in simi- lar patients treated at Dana-Farber and the survival benefit associ- ated with integrated palliative care in patients with lung cancer.20 With 2:1 randomization, the sample size needed to detect the esti- mated effect size was calculated to be 160 - 107 in the standard care arm and 53 in the arm with geriatric consultation - assuming 80% power and a one-sided type I error rate of 5%. This sample size was recalculated from 152 (76 per group), which was original- ly calculated for 1:1 randomization. The study was approved by the Dana-Farber/Harvard Cancer Center Office for the Protection of Human Research Subjects.
Geriatric consultation intervention
Patients who were assigned to the intervention received embed- ded geriatric consultation with a licensed geriatrician in addition to their standard oncologic care managed by their hematologic oncologist. The embedded geriatrics clinic is located within Dana- Farber on the same floors as the hematologic malignancies clinics. Of note, embedded geriatric consultation had been available for patients referred from the leukemia clinic (without prior GA screening and randomization) for 2 years preceding the start of the trial.
After assignment, patients from leukemia, lymphoma, and myeloma clinics were scheduled with a geriatrician either on the same day as their follow-up oncology consultation or at a different time in accordance with the patient’s schedule and appointment availability; we intended for the patients to be seen as early as pos- sible but did not require a specific time period for the first visit. Consistent with other trial designs evaluating the effectiveness of integrated subspecialty care,20 the geriatrician provided further management and interventions individualized to the patient based on clinical judgment and best-available evidence; no pre-specified interventions were required. If indicated, geriatricians communi- cated with the patient’s primary care provider and utilized referral systems (e.g., physical therapy, psychiatry) already established at Dana-Farber. Follow-up appointments were encouraged, but not required.
In keeping with routine care provided by geriatricians, the geri- atrician conducted a GA for every patient encountered. To charac- terize the interventions recommended by the geriatrician, a con- tent analysis of the geriatricians’ notes was conducted.21 For each patient we classified whether the geriatrician recommended an intervention targeting one or more domains described in ASCO’s Guideline for Geriatric Oncology: (i) function and falls; (ii) comor- bidity and polypharmacy; (iii) cognition; (iv) depression/mood; and (v) nutrition.8 Recommended interventions could include counseling, recommendations for non-pharmacological interven- tions, pharmacological interventions, and referrals to other special- ties or allied healthcare. For each patient, all geriatricians’ notes through the 1-year follow-up period were reviewed, and new interventions were only counted once.
Outcome measures
The primary outcome of this study was 1-year overall survival from the time of initial hematologic oncology consultation. Vital status was confirmed by a combination of chart review and calls to patients’ primary care providers.
Secondary outcomes were assessed via chart review and includ- ed the number of emergency department visits, the number of unplanned hospital admissions, and the number of days spent in the hospital22 within 6 months after patients’ initial consultations at Dana-Farber. Having any end-of-life (EOL) goals-of-care discus-
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