Table 1.

Summary of pivotal RCTs evaluating the impact of GA and GA-driven interventions.

Study	Population	Intervention	Comparison	Outcome Measures	Significant Results
GAIN [3] N = 605	- Age ≥65 - Planned for chemotherapy ± targeted tx. 1 US center	GA, SPICES, and CARG-TT. GA assessed domains of functional status, comorbidity, cognitive/psychological state, social activity/support, and nutritional status. SPICES evaluated common geriatric syndromes: sleep disorders, problems with eating/feeding, incontinence, confusion, evidence of falls, and skin breakdown. Results reviewed and interventions directed by geriatric trained MDT.	Results reviewed by oncologist.	1°: Gr ≥ 3 tx toxicity. 2°: - Chemo dose modifications and/or d/c. - ACP completion. - Healthcare utilization. - OS.	↓ Gr ≥ 3 tx toxicity in intervention arm (50.5% vs. 60.6%, p = 0.02). ↑ in ACP completion in intervention arm (28.4% vs. 13.3%, p < 0.001).
GAP70+ [4] N = 718	- Age ≥70 - Stage III/IV - Planned for tx with high risk of toxicity - ≥1 GA domain impairment. Multiple US centers	GA assessing domains of physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. GA summary and recommended interventions developed by study team for oncologist review.	No GA summary or recommendations provided to oncologist.	1°: Gr 3–5 tx toxicity. 2°: - Tx intensity. - OS.	↓ Gr 3–5 tx toxicity in intervention arm (51% vs. 71%, aRR 0.74, p = 0.0001). ↑ likelihood of reduced tx intensity (aRR 1.38, p = 0.015).
GERICO [5] N = 142	- Age ≥70 - Stage II-IV colorectal cancer - Planned for adjuvant or 1st line palliative chemo - Life expectancy ≥3 mo - ECOG 0–2 - Vulnerability identified using G8 screening tool. 2 Danish centers	GA assessing domains of co-morbidity, psycho-cognition, nutrition, and functional and physical status. Results reviewed and interventions directed by study team.	SOC by oncology team.	1°: Chemo completion with no additional dose reductions or delays (although oxaliplatin excluded). 2°: - Chemo dose reductions and/or delays. - AEs. - DFS. - PFS. - OS. - Colorectal cancer mortality.	↑ chemo completion without additional dose reductions or delays in intervention arm (45% vs. 28%, p = 0.04). Difference most prominent with adjuvant chemo (p = 0.01) versus palliative (p = 0.75). ↓ subsequent dose reductions in intervention arm (28% vs. 45%, p = 0.04).
INTEGERATE [6] N = 154	-Age ≥70 - Planned for systemic tx. 3 Australian centers	GA assessing domains of co-morbidities, medications, physical/cognitive/psychological social functioning, frailty, falls, nutrition, sensory impairment, immunization status, ACP, and chemo toxicity risk. Results reviewed and interventions directed by dual trained GO during serial visits.	SOC by oncology team.	1°: Change in hrQoL. 2°: - Functional status. - Mood. - Nutrition. - Anticancer tx modification. - Healthcare utilization. - Institutionalization. - OS.	↓ decline in hrQoL with intervention (overall main effect p = 0.039, effect size = 0.38). ↑ ED presentations (multivariable-adjusted incidence RR 0.59, p = 0.005), unplanned hospitalizations (multivariable-adjusted incidence RR 0.60, p = 0.007), and unplanned hospital days (multivariable-adjusted incidence RR 0.77, p < 0.0001).
5C [53] N = 350	- Age ≥70 - Referred for 1st or 2nd line adjuvant or palliative systemic tx. -Life expectancy >6 mo - ECOG 0–2. 8 Canadian centers.	GA assessing domains of functional status, cognition, nutrition, medications, co-morbidities, mobility, and falls. Results shared with oncologist. Results reviewed and interventions directed by team of GO fellows, a geriatrician, and a nurse.	SOC by oncology team.	1°: QoL. 2°: - Functional limitations. - Gr 3–5 tx toxicity and/or d/c - Tx modification. - OS.	No significant difference in any 1° or 2°. outcome.
Dumontier et al. [57]. N = 160	- Age ≥75 -Hematologic malignancy -not eligible for transplantation -initial consultation with hematologist-oncologist -Frail and pre-frail patients 1 US center	Consultation by a geriatrician. GA included assessment of function, falls, comorbidity, polypharmacy, cognition, mood, and nutrition.	Standard of care	1°: OS at 1 year. 2°: -unplanned healthcare utilization within 6 months (ED visits, unplanned hospitalization admissions, days in hospital). -documented end-of-life goals of care discussions.	No difference in survival at 1 year (18.3% vs. 21%, p = 0.65). Increased odds of EOL goals-of-care discussions (OR 3.12). No difference in ED visits, hospital admissions or duration of hospital stay.

Abbreviations: AE = adverse event; aRR = adjusted risk ratio; CARG-TT = Cancer and Aging Research Group chemotherapy toxicity tool; chemo = chemotherapy; d/c = discontinuation; DFS = disease-free survival; ECOG = Eastern Cooperative Oncology Group; ED = Emergency Department; GA = geriatric assessment; GO = geriatric oncologist; Gr = grade; hrQoL = health-related quality of life; MDT = multidisciplinary team; mo = months; OR = odds ratio; OS = overall survival; PFS = progression-free survival; QoL = quality of life; RR = rate ratio; SOC = standard of care; tx = treatment; US = United States; 1° = primary; 2° = secondary; ↓ = decreased; and ↑ = increased.