Table 1.

Older-adult specific studies meeting inclusion criteria and primary functional status results (N=17).

Age inclusion criteria	Study/Quality assessment scorea	Study design	Sample (cancer type(s), stage)	Overall N (systemic therapy n)	Age (age 65+ n if available or age summary statistic – mean/median)	Systemic cancer treatment(s)	Primary measure(s) of function status	Assessment time points	Definition of functional change	Change in functional status during treatment	Association of patient characteristicsb with functional status change
Age ≥60	Klepin 201619/8	Single center observational cohort (US)	AML	49	Mean age 70 (SD 2); 57.1% age 60-69, 34.7% 70-79, 8.2% ≥80	Chemo	Pepper Assessment Tool for Disability (ADL, IADL, mobility), SPPB, grip strength	Pretx (hospitalization for induction chemo), 8 wks after discharge	Decline using standard cutoffs	-IADL dependence worsened (1.4 baseline vs 2.1 follow-up, p<0.001) -SPPB worsened (7.5 vs 5.9, p=0.02) -Grip strength declined (men: 38.9 vs 34.2, p<0.001; women: 24.5 vs 21.8, p=0.007)	-Unfavorable cytogenetic risk score (p=0.05) and receipt of the most intense chemo (cytarabine/daunorubicin/etoposide) (p=0.03) were associated with ADL decline -Higher BMI (p=0.03) and unfavorable cytogenetic risk score (p=0.01) were associated with IADL decline -Depressive symptoms at baseline and follow-up were associated with decline in SPPB score (p=0.03) -Receipt of the most intense chemo (p=0.02) was associated with decline in SPPB gait speed -Higher baseline cognition score was associated with improvement in SPPB balance (p=0.05) -Remission status was not associated with functional decline
Age ≥65	Doni 201120/9	Multicenter observational cohort (Italy)	All types, all stages	578	Mean age 72.6 (SD 5.0), median 71.9 (range 64.9-100)	Chemo	ADL, ECOG PS	Pretx, before each cycle (for at least 12 wks)	Longitudinal modeling	-Mean ADL score worsened up to wk 20 -Progressive worsening of ECOG PS starting from wks 11-13 (pretx: 49% ECOG 0, 41% ECOG 1, 9.8% ECOG ≥2; at follow-up: 46.6% ECOG 0, 42.2% ECOG 1, 11.1% ECOG ≥2)	-At wk 12, hemoglobin change of at least 1 g/dl was associated with ADL decline (p<0.05) -Stage and PS were not associated
Age ≥65	Gajra 201821/10	Multicenter RCT (US)	Breast, stage I-III	145	Median age 71; 40% age 65-69, 54% 70-80, 6% >80	Adjuvant chemo (AC, CMF) vs capecitabine	Subjective Significance Questionnaire (self-reported change in physical condition), EORTC QLQ-C30 PF	Midtx; 1, 12, 18, 24 mos after EOT	Self-report worsening physical condition	-At mid-treatment, 25% reported worse, 49% same, and 26% improved physical condition -At 1 yr, 6% reported worse, 37% same, 57% improved physical condition	-Low preference for chemo was associated with worse physical condition at mid-treatment (p=0.005) but not at the other time points -No association between chemo preference and EORTC QLQ-C30 PF
Age ≥65	Goodwin 20061/10	Multicenter observational cohort (US)	Solid tumor, all stages	26	Mean age 71 (SD 5, range 65-82)	Chemo	Short Functional Dependence Scale ADL and IADL	Pretx, chemo visits 1-9	Longitudinal modeling	-Not reported	-Older age, cancer type, surgery, radiation, and lower hemoglobin were associated with higher functional dependence across visits
Age ≥65	Hurria 201922/10	Multicenter RCT (US)	Breast, stage I-III	256	Mean age 71.9 (SD 4.7, range 65-85)	Chemo	EORTC-QLQ-C30 PF	Pretx; posttx; 12 mos after chemo initiation	-Decline from pretx to posttx: ≥10 point decrease from pretx to posttx, -Resilience (only those declined): returned to within 10 points of pretx PF -Decline at 12 mos: ≥10 point decrease from pretx to 12 mos after -Resistance to decline: <10 point decrease from pretx to posttx and 12 mos after	-Decline from pretx to posttx: 42% (median decline 20 points, range 11.7-73.3) -Resilience at 12 mos: 47% recovered -Decline at 12 mos: 30% (median decline 20 points, range 13.1-53.3) -Resistance to decline: 49.6%	-Decline from pretx to posttx was associated with baseline fatigue (OR 2.37, p=0.02). Comorbidity was not associated at posttx. -Resilience at 12 mos was associated with being married (OR 2.52, p=0.04), having <4 positive nodes (OR 3.57, p=0.048), and no pre-treatment appetite loss (OR 3.65, p=0.02) -Decline at 12 mos was associated with being unmarried (OR 1.98, p=0.01) and pretreatment dyspnea (OR 2.37, p=0.007). Fatigue, having <4 positive nodes, and older age were not associated with decline at 12 mos. -Resistance to decline was associated with no pretreatment fatigue (OR 2.49, p=0.01) and no dyspnea (OR 1.94, p=0.03). Comorbidity was not associated.
Age ≥65	Manokumar 201623/9	Single center observational cohort (Canada)	Prostate, stage IV	36	First line: Mean age 77.3 (SD 4.5); Second line: Mean age 71.4 (SD 6.2)	Docetaxel	OARS-IADL, TUG, timed chair stands, handgrip strength, falls (≥1)	Pretx, q3 mos until posttx	Change score	1st-line chemo -IADL: 21% improved, 52% stable, 28% declined -TUG: 22% improved, 39% stable, 39% declined -Timed Chair Stands: 17% improved, 42% stable, 42% declined -Handgrip strength: 11% improved, 61% stable, 29% declined -Falls: 38% experienced one fall	-Vulnerable Elders Survey (VES-13) score ≥3 was associated with greater increase in timed chair stand score
Age ≥65	Miaskowski 201724/9	Multicenter observational cohort (US)	Breast, GI, GYN, lung; all stages	363	Mean age between 70.7 to 72.7 (SD 5.4-6.0)	Chemo	SF-12 PCS	Baseline (chemo within the prior 4 wks), 1 wk and 2 wks post-chemo, then repeat for the subsequent cycle	Change score	-Three classes based on latent class analysis (above, below, and well below the normative norm of individuals aged 65-74) -PCS score remained relatively stable over 2 cycles of chemo	-Unemployment (p<0.001), lower income (p=0.002), and a history of heart disease (p=0.001) were associated with being in the below and well below classes -Exercise on a regular basis (p<0.001), self-reported back pain (p<0.001), lower hemoglobin (p=0.002), and self-reported depression (p=0.028) were associated with being in the well below class -Age, gender, cancer diagnosis, time since cancer diagnosis, number of metastatic sites, number and types of prior cancer treatments, and chemo cycle length were not associated with latent class membership
Age ≥65	Rier 20182/11	Single center observational cohort study (Netherlands)	All types, all stages	142	Median age 72 (range 69-78)	Chemo	IADL	Pretx, midtx, posttx	IADL independence: ≥8 points; IADL decline: ≥3 points decline at posttx or ≥2 points decline at 1 year posttx	-IADL independence: Pretx (63.9%), posttx (56.3%) -IADL decline: 11.5%	-Age (p=0.05), impaired cognition (0.05), refractory or progressive disease at posttx (vs complete remission, p=0.003), and severe sarcopenia (vs normal, p=0.05) were associated with IADL decline (all univariable analyses) -None were associated with decline on multivariable analysis
Age ≥65	Verelst 201125/11	Multicenter RCT (Netherlands)	Multiple myeloma, all stages	284	Median age 72 (range 65-84)	Melphalan/prednisone, melphalan/prednisone/thalidomide	EORTCQLQ-C30 PF	Pretx, cycle 3 (3 mos), cycle 8 (9 mos), 12 mos, 18 mos	Change score	-EORTC QLQ-C30 improved in both arms over time, though this was in favor of the 2-drug regimen early during induction phase	-Female sex was associated with lower scores on EORTC QLQ-30 PF (p=0.003)
Age ≥65	Wong 201826/10	Multicenter observational cohort (US)	Breast, GI, GYN, lung; all stages	363	Mean age 71.4 (SD 5.5)	Chemo	SF-12 PCS	Baseline (chemo within the prior 4 wks), 1 wk and 2 wks post-chemo, then repeat for the subsequent cycle	Longitudinal modeling	-PCS scores decreased slightly (0.21 points, p<0.01) at each subsequent assessment	-Higher morning fatigue (p=0.04) and lower enrollment PCS scores (p=0.01) were associated with decrease in PCS score over time -Age, sex, ethnicity, education, marital status, living alone, employment status, child care responsibilities, BMI, smoking status, hemoglobin, KPS, comorbidity, regular exercise, cancer type, time since cancer diagnosis, prior cancer treatments, metastatic disease, chemotherapy toxicity index, cycle length, evening fatigue, morning energy, evening energy, pain, anxiety, and attentional function were not associated
Age ≥65	Xue 201527/7	Single center RCT (China)	NSCLC, stage IIIB-IV	24	Mean age 73 (SD 5.3, range 65-83)	Chemo	EORTC QLQ-C30 PF	Pretx (day 1 prior to chemo); 7d, 21d, 42d, 63d post-chemo	Change score	-No change in functioning scale among function-independent and mildly function-impaired patients -For function-dependent patients, PF improved	-Worse baseline functional status was associated with improvement in PF
Age ≥70	Chakiba 201928/11	Multicenter observational cohort (France)	Colon, pancreatic, stomach, ovarian, bladder, prostate, lung, NHL, cancer of unknown primary; all stages	292	Median age 77 (range 70-93); 36% age 70-75, 35% 76-80, 22% 81-85, 7% >85	Chemo	ADL	Pretx, before cycle 2	Decline: 0.5 point decrease	-16% declined, 10% improved, 73% stable ADL score	-Abnormal G8 (≤14) was associated with functional decline (OR 4.3, 95% CI 1.28-14.92; p=0.018) in multivariable model -Age, sex, tumor type, stage, neutrophil count, platelet count, creatinine clearance, albumin, and CRP were not associated
Age ≥70	Fiteni 201629/10	Multicenter RCT (France)	NSCLC, stage III-IV	361	Mean age 77.1 (range 70-88); 49.9% age <77, 50.1% ≥77	Carboplatin/paclitaxel vs gemcitabine vs vinorelbine	EORTC QLQ-C30 PF	Pretx, 6 and 18 wks	PF MCID: 5 points; time to deterioration	-Median time to deterioration: doublet chemo 2.04 mos (95% CI 1.87-3.88) vs monotherapy 1.71 (95% CI 1.58-1.91), p=0.01	-Doublet chemo was associated with longer time to PF deterioration (HR 0.57, 95% CI 0.42-0.78, p=0.008) -Female sex (HR 1.53, 95% CI 1.09-2.15, p=0.01) and CCI score >2 (HR 1.50, 95% CI 1.08-1.12, p=0.002) were associated with shorter time to PF deterioration -Age, PS, smoking status, BMI, MMSE, ADL, stage, and histology were not associated with time to PF deterioration
Age ≥70	Hoppe 201330/12	Multicenter observational cohort (France)	Colon, pancreatic, stomach, ovarian, bladder, prostate, lung, non-Hodgkin lymphoma, unknown primary origin, all stages	364	Median age 77.3 (range 70-93)	Chemo	Katz ADL	Pretx, before cycle 2	ADL decline: decrease of ≥0.5 in total score	-Decline: 16.7% (median 0.5 points, range 0.5-3) -Improvement: 10.7% (median 0.5 points, range 0.5-2.5)	-High GDS-15 (OR 2.16, p=0.03) and low IADL (OR 2.87, p=0.04) were associated with decline -Age, sex, PS, weight loss, BMI, leukocytes, platelet count, creatinine, CRP, hemoglobin, albumin, tumor type, disease extension, CIRS-G, MAX2 index, ADL, MNA, MMSE, and GUG were not associated with decline
Age ≥70	Kenis 201731/11	Multicenter observational cohort (Belgium)	Breast, CRC, ovarian, lung, prostate, hematologic malignancy; all stages	439	Mean age 75 (range 70-95)	Chemo	Katz ADL, Lawton IADL	Pretx, 2-4 mos after chemo	ADL decline: change of ≥2 in total score, IADL decline: change of ≤1 in total score	-ADL decline: 19.9% -IADL decline: 41.3%	-Abnormal nutritional status (OR 2.02, p=0.007) and baseline IADL dependency (OR 1.76, p=0.037) were associated with ADL decline -Disease status (progression/relapsed vs new diagnosis; OR 0.59, p=0.014) was associated with IADL decline -Age, geriatric screening tools, ECOG PS, fall, pain, polypharmacy, living situation, comorbidity, fatigue, baseline ADL, cognition, depression, cancer type, and treatment were not associated with both ADL and IADL decline
Age ≥70	Morikawa 201832/8	Single center observational cohort (Japan)	NSCLC, stage III-IV	18	Median age 74.5 (range 70-82)	Chemo, targeted therapy	Physical activity (accelerometer)	Pretx (prior to hospitalization); during hospitalization; 1, 2, 3 wks after discharge	Hospitalization-associated physical inactivity: decreased mean daily steps both during hospitalization and during the 1st wk as compared with mean daily steps at baseline	-50% walked fewer daily steps during hospitalization and did not recover to baseline level at 1 wk after discharge	-Cachexia and longer hospitalization (≥8 vs <8 days) were associated with hospitalization-associated physical inactivity
Age ≥70	Naito 201733/8	Single center observational cohort (Japan)	NSCLC, stage III-IV	30	Median age 74 (range 70-82)	Chemo, targeted therapy	Barthel ADL	Pretx, each hospital visit	Disabling event defined as decrease in Barthel ADL >10 points; disability free survival	-90% were disabled at the cutoff date -Disabling events: stair climbing (100%), morbidity (96%), bathing (89%), toilet use (56%), and transferring (41%)	-Cachexia was associated with shorter disability-free survival (7.5 vs 17.1 mos, p<0.05) and longer post-disability survival (2.5 vs 0.7 mos, p<0.05)

Abbreviations: ADL, activities of daily living; AC, cyclophosphamide/doxorubicin; AML, acute myeloid leukemia; BMI, body mass index; chemo, chemotherapy; CIRS-G, Cumulative Illness Rating Scale-Geriatrics; CMF, cyclophosphamide/methotrexate/fluorouracil; CRC, colorectal cancer; CRP, C-reactive protein; d, day; ECOG, Eastern Cooperative Oncology Group; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30; EOT, end of treatment; GDS-15, Geriatric Depression Scale-15; GI, gastrointestinal; GUG, Timed Get Up and Go; GYN, gynecological; IADL, instrumental activities of daily living; KPS, Karnofsky Performance Status; MCID, minimal clinically important difference; midtx, midtreatment; MMSE, Mini-Mental State Examination; MNA, Mini-Nutritional Assessment; mo, month; mos, months; NHL, non-Hodgkin lymphoma; OARS, Older American’s Resource Scale; PCS, Physical Component Summary; PF, physical functioning; posttx, posttreatment; pretx, pretreatment; PS, performance status; RCT, randomized controlled trial; NSCLC, non-small cell lung cancer; SD, standard deviation; SF, short-form; vs, versus; wk, week; wks, weeks; TUG, Timed Up and Go; tx; treatment; yr, year; yrs, years

^aQuality assessment performed using the National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, which consists of 14 criteria.

^bWe listed patient characteristics that are associated with functional change as well as those that are not associated. We did not list patient characteristics if they were only included as covariates without a reported result.