Table 2.

Non-older adult specific studies meeting inclusion criteria and primary functional status results (N=27).

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 functional status	Assessment time points	Definition of functional status change	Change in functional status during treatment	Association of patient characteristicsb with functional status change
Alibhai 201534/10	Multicenter observational cohort (Canada)	AML	237	59% age <60 (median age 52.9); 41% ≥60 (median age 69.7); range 21-81	Induction daunorubicin, cytarabine	2MWT, chair stands, grip strength, IADL	Pretx; 4-6, 9-12, 13-16 wks; 6, 8, 10, 12 mos	2MWT MCID: 59 ft, grip strength MCID: 4.5 kg (MCID not reported for chair stands and IADL)	-2MWT (p<0.001), chair stands (p<0.001), and IADLs (p=0.003) improved -No change in grip strength	-Younger age was associated with greater recovery in chair stands (p=0.048) -Gender, smoking status, baseline PS, and hemoglobin were not associated with change in physical function
Bergman 199135/9	Single center observational cohort (Sweden)	SCLC, all stages	62	Mean age 66 (range 36-80); 35% age ≥70	Chemo	Sickness Impact Profile physical index (ambulation, body care/movement, mobility)	Pretx; 3, 6, 9, 12 mos	Correlation with physical index change score	-Body care/movement subscale worsened 5 points at 3 mos and 6.1 points at 6 mos (p<0.05); no difference at 12 mos -No change in ambulation or mobility	-Characteristics associated with worsening physical index: worsening ECOG/WHO PS, EORTC pain, EORTC appetite (p<0.01); tumor non-response, cisplatin-containing regimen, neutropenia (p<0.05) -Age, sex, depression, hair loss, and nausea were not associated
Bezjak 200636/13	Multicenter RCT (global)	NSCLC, stage IIIB-IV	425	Median age 61	Erlotinib vs placebo	EORTC QLQ-C30 PF	Pretx, q4 wks during tx, 4 wks posttx, q12 wks until EOT	PF decline: ≥10 point decrease, improvement: ≥10 point increase, stable: <10 point change	-Erlotinib: 51% declined, 31% improved, 18% stable PF	-Only treatment with erlotinib was associated with improvement in PF (p=0.006) -Age, sex, ethnicity, PS, prior treatment, histology, and smoking history were not associated
Chen 200337/9	Single center observational cohort (US)	Solid tumor, non-leukemic hematologic malignancy, all stages	37	Mean age 75.6 (range 70-87); 38% age 70-74, 54% 75-80, 8% 81-87	Chemo	IADL, ECOG PS	Pretx, EOT (or at 6 mos)	Change score	-Mean 1.44 point decline in IADL score (p=0.04) -No change in ECOG PS	-Severe chemotherapy toxicities were associated with decline in IADL (change score −2.93 vs −0.17; p=0.03) and ECOG PS (change score 0.56 vs −0.11; p = 0.03)
de Jong 200638/12	Multicenter observational cohort (Netherlands)	Breast, stage I-III	157	Mean age 47.3 (SD 8.8, range 25-70)	Adjuvant CMF or doxorubicin-containing regimen	Multidimensional Fatigue Inventory reduced activity subscale	Cycle 1, 3, 5; 4 and 12 wks after last cycle	Longitudinal modeling	-Activity level stable during study period	-Older age and not having children were associated with lower activity level over time -Mastectomy (vs lumpectomy), longer duration of radiation, and fewer total chemotherapy treatments were associated with lower activity level -Chemotherapy type, marital status, education, having a job, hemoglobin, and time between surgery and chemotherapy were not associated with change in activity level
Dodd 200139/10	Multicenter RCT (US)	All types, all stages	93	Mean age 55.4 (SD 14.6)	Chemo (RCT of two mouthwashes for mucositis)	Patient-reported KPS	Pretx, end of cycle 3	Longitudinal modeling	-Pretx mean KPS 84.8 -End of cycle 3 mean KPS 82.7	-Pretx KPS, older age, worse pain, and worse fatigue were associated with worse KPS at the end of cycle 3 -Sleep insufficiency was not associated
Dodd 201040/8	Multicenter RCT (US)	Breast, stage I-III	112	Mean age 50 (SD 9.3)	Chemo (RCT of exercise intervention during chemo, after chemo, vs usual care)	Patient-reported KPS	Before cycle 2, EOT, 1 yr	Association with symptom clusters (pain, fatigue, sleep disturbance, depression) at each assessment	-Not reported	-Before cycle 2, All Low symptom cluster was associated with better KPS vs Moderate cluster (p=0.002) -At EOT, All Low cluster was associated with better KPS vs all other clusters (p<0.0001) -At 1 yr, Mild cluster associated with better KPS vs Moderate and All High clusters (p<0.005)
Doorenbos 200641/10	Multicenter RCT (US)	Solid tumor, all stages	237	Mean age 60 (SD 10, range 31-87)	Chemo (RCT of cognitive behavioral theory guided intervention vs usual care)	SF-36 PF	Baseline; 10, 20, 32 wks	Longitudinal modeling	-Baseline mean PF 64.2 (SD 29.5), wk 20 mean PF 70.6 (SD 28.1) -At wk 20, women with breast cancer had higher PF than women with lung cancer (p=0.001); men with lung cancer had higher PF than women with lung cancer (p=0.02)	-At wk 20, patients with a higher number of chronic health conditions (vs low number) benefited more from the effect of the intervention on PF (p=0.02) -Lower depressive symptoms and lower symptom limitations were associated with increased intervention effect on PF -Age, sex, stage, and tumor type were not found to mediate intervention effect on PF
Fallowfield 200242/12	Multicenter RCT (global)	Solid tumor or non-myeloid hematologic malignancies, all stages	375	Epoetin arm: Mean age 58.1 (SD 14.2, range 18-84) Placebo arm: Mean age 59.2 (SD 14.3, range 21-88)	Non-platinum chemo (RCT of epoetin alfa vs placebo)	CLAS daily activities, SF-36 PCS	Randomization; 4, 16, 28 wks	Change score at last available assessment	-Mean CLAS daily activities change score: Epoetin arm 7.78 vs placebo arm −1.96 (p<0.04). -No difference in mean SF-36 PCS change score by arm: Epoetin arm 1.27 vs placebo arm 0.05 (p=0.33)	-Higher hemoglobin level was associated with higher CLAS daily activities and SF-36 PCS over time (p<0.01) -Higher baseline endogenous erythropoietin was associated lower CLAS daily activities over time (p<0.05) -Lower reticulocyte count and pre-study transfusion dependency were associated with higher SF-36 PCS over time (p<0.05) -Older age was associated with lower SF-36 PCS score over time (p<0.01) -Age, race, and disease progression were not associated with change in CLAS daily activities -Sex and disease progression were not associated with change in SF-36 PCS
Frodin 201143/9	Single center observational cohort (Sweden)	Myeloma, lymphoma, testicular, sarcoma, AML; all stages	96	Mean age 54 (SD 12)	auto-SCT	EORTC QLQ-C30 PF	Pretx; wkly during wks 1-4; monthly during mos 2, 3; 6 mos; q6 mos up to yr 3	Longitudinal modeling	-At wk 2, 42% declined in PF -PF improved back to baseline by month 2	-At wk 2, a diagnosis of myeloma (vs lymphoma) was associated was better PF (p=0.001)
Frodin 201544/10	Single center observational cohort (Sweden)	Any hematologic malignancy, all stages	94	Mean age 48	Allogenic SCT, reduced intensity conditioning	EORTC QLQ-C30 PF	Pretx, wkly during wks 1-4, monthly during mos 2, 3; 6 mos; q6 mos up to yr 3	Change score	-Pretx PF mean: 81 -At 3 wks, change score −36 (p<0.05 compared with pretx) -At 3 mos, change score −20 (p<0.05) -At 1 yr, change score −8 -At 3 yrs, change score −5	-Extensive chronic GVHD was associated with worse PF compared with limited chronic GVHD and no chronic GVHD at 1.5, 2, and 2.5 yrs (all p<0.01)
Gaston-Johansson 201545/11	Single center observational cohort (US)	Breast, all stages	30	Mean age 52.7 (SD 10.2, range 32-72)	Chemo	FACT-Breast physical and functional well-being	Pretx, midpoint, EOT	Longitudinal modeling	-Physical and functional well-being decreased at midpoint and EOT compared with pretx (all p<0.001)	-Worst pain intensity was associated with worse functional well-being at EOT -No association with age or stage
Given 200246/10	Multicenter RCT (US)	Solid tumor and NHL, all stages	113	Mean age 58 (SD 10.5)	Chemo (RCT of nursing symptom management intervention vs usual care)	SF-36 Physical role functioning	Baseline (within 8 wks of chemo initiation); 10, 20 wks	Longitudinal modeling	-Intervention arm: Mean physical role functioning score 11 (SD 22) at baseline, 50 (SD 41) at 20 wks -Control arm: Mean physical role functioning score 11 (SD 22) at baseline, 31 (SD 36) at 20 wks	-Intervention was associated with improved physical role functioning at 20 wks (mean score 50 vs 31) -Diagnosis of breast cancer (vs non-breast cancer) was associated with improved physical role functioning at 20 wks
Greimel 200647/10	Multicenter RCT (Germany, Austria)	Ovarian, stage IIB-IV	416	Mean age 56.6 (SD 10.1)	Cisplatin/paclitaxel vs carboplatin/paclitaxel	EORTC QLQ-C30 PF	Pretx; cycle 2, 4; EOT; q6 mos	Longitudinal modeling	-Mean PF change score 9.4 (carboplatin/paclitaxel) vs 1.7 (cisplatin/paclitaxel)	-Carboplatin/paclitaxel arm had better EOT PF -Characteristics associated with worse PF over time: anemia, neurotoxicity, GI toxicity, older age -Hematologic toxicity, pain, and treatment arm were not associated with change in PF over time
Kim 201048/8	Single center observational cohort (Korea)	Diffuse large B cell or follicular lymphoma, all stages	32	Mean age 55.9 (range 21-79)	Chemo	SF-36 PCS	Pretx, 2nd visit during chemo, last visit after cycle 6	PCS score <40	-Pretx: 12 patients had a PCS score <40 −2nd visit: 12 patients had a score <40 -Last visit: 5 patients had a score <40	-Neuropathy at 2nd visit was associated with lower PCS score at the last visit (PCS score 44.5 for neuropathy vs 49.9 for non-neuropathy, p=0.02)
Kinsey 201849/12	Multicenter RCT (global)	NSCLC, stage III-IV	236	37.5% age ≥ 65	Chemo	Stair climb power	Pretx, day 84	% Loss	≥10% loss: 31% 0 to <10% loss: 18% ≥0 to <10% gain: 10%, ≥10% gain: 31%	-Taxane (vs non-taxane therapy, p=0.023) and prior smoking (vs current use, p=0.027) were associated with functional decline -Prior weight loss, disease response, lean body mass, ECOG PS, disease stage, age, gender, and comorbidities were not associated with functional decline
Land 200450/12	Multicenter RCT (US, Canada)	Breast, stage I-II	160	50.6% age ≤ 49, 32.5% 50-59, 16.9% ≥ 60	Chemo	SF-36 return to normal activity	Pretx, start of each chemo cycle (several time points from wk 3-52)	Change score	-Return to normal activity score did not change during chemotherapy	-Lumpectomy and radiation (vs mastectomy) were associated with lower return to normal activity score (1.11 points lower, p=0.02) -Chemotherapy (CMF vs AC), tamoxifen, surgery, tumor size, and age were not associated with return to normal activity score
Mohamedali 201251/10	Single center observational cohort (Canada)	AML	103	Younger: Median age 52.0 (range 21-59) Older: Median age 69.7 (range 60-80)	Induction daunorubicin, cytarabine	EORTC-QLQ-C30 PF, handgrip strength, timed chair stands, 2MWT	Time of dx; 4-5 wks, 8-10 wks, 12-16 wks (after each cycle of chemo)	Change scores; MCID 10 points	-No statistically significant change in EORTC PF -Handgrip strength decreased	-Older patients had greater magnitude of decline in handgrip strength (younger: 30.7 to 28.0; older: 31.1 to 25.0) -Younger patients had improved chair stands over time (22.3 to 29.0, p<0.001) but older adults did not (20.3 to 19.8, p=0.36) -Both groups improved on the 2MWT (p<0.001) -Younger patients had less decline or greater improvement in all three PF tests over time compared to older patients
Morita 200352/10	Multicenter RCT (Japan)	NSCLC, stage IIIB-IV	377	Median age 61 (range 35-75)	Chemo	QOL-ACD physical well-being, ECOG PS	Pretx; day 8, 15, 22	Change scores	-Maximum decrease in score for each domain was observed at wk 1 -More severe deterioration of PS was observed in wks 1 and 2, while a noticeable number of patients experienced improved PS in wk 4	-Nausea/vomiting (p<0.001), anorexia (p<0.001), diarrhea (p<0.001), and PS deterioration (p=0.001) were associated with decline of physical well-being -Age, gender, and treatment arm were not associated
Oechsle 201153/9	Single center observational cohort (Germany)	All types, stage II	53	Median age 58 (range 29-76)	Chemo	Questionnaire for Measurement of Habitual Physical Activity (work, sports, leisure indices), EORTC-QLQ-C30 PF, International Physical Activity questionnaire	Baseline; 4 wks	Change score	-Work index: decreased from 2.25 to 0.56 (p<0.001) -Sports index: decreased from 2.91 to 2.47 (p<0.001) -Leisure time index: increased from 2.81 to 3.01 (p<0.01) -Median time of sportive activities decreased (1.6 hour to 0.8 hour, p<0.01) -No change in EORTC-QLQ-C30 PF	-Sports index prior to cancer diagnosis was higher among men (p<0.05) but no difference in sports index during chemo by gender -No gender differences in EORTC QLQ-C30 PF
Revicki 201254/9	Multicenter RCT (global)	Melanoma, stage III-IV	676	Mean age 56.2 (SD 57)	Ipilimumab/gp100 vs ipilimumab alone vs gp100 alone	EORTC-QLQ-C30 PF	Pretx; 12 wks	No change: 0–5 points; a little change: 5–10 points; moderate change: 10–20 points; very much >20 points	Change scores: -Ipilimumab plus gp100: −6.2 -Ipilimumab alone: −5.1 -Gp100 alone: −10.1	-Older and younger patients (<65 vs ≥ 65 yrs) had similar PF decline in the ipilimumab plus gp100 and ipilimumab alone groups
Shallwani 201655/8	Single center observational cohort (Canada)	NSCLC, stage IIIA-IV	47	Mean age 63.3 (SD 12.2)	Chemo	SF-36 PCS, 6MWT, 1 minute chair rise test, grip strength	Pretx, post-cycle 2	SF-36 MCID: 5 units; 6MWT MCID: 54 meters. Longitudinal modeling	-SF-36 PCS worsened overall: Pretx 40.8, posttx 38; p=0.02. 20% had clinically significant improvements; 33% deteriorated −6MWT worsened overall: Pretx (454.5), posttx (414.3); p<0.01. 9% had clinically significant improvements; 14% deteriorated -Chair rise test stable: Pretx (21.4), posttx (20.7); p<0.25 -Grip strength worsened: Pretx (27.4), posttx (26.5); p=0.03	-Nutritional status, fatigue, and 6MWT were not associated with SF-36 PCS
Timilshina 201956/9	Multicenter observational cohort (Canada)	AML	71	Median age 52 (IQR 41-58)	Intensive chemo	EORTC QLQ-C30 PF, grip strength, 10 timed chair stands	Pretx; 11 time points over 3 yrs	Recovery defined as reaching 1 MCID unit for each outcome (EORTC QLQ-C30 MCID: 10, FACT-F MCID: 4, grip strength MCID: 4.5 kg, 6MWT MCID: 54 meters, timed chair stand MCID: 3.4 seconds)	-EORTC QLQ-C30 PF unchanged: Baseline (80.6), 12 mos (85.2), 24 mos (82.5), 36 mos (90.0) -EORTC QLQ-C30 PF: 72% returned to normal at 1 yr and 77% at 3 yrs -Grip strength unchanged: Baseline (30.3), 12 mos (31.2), 24 mos (31.8), 36 mos (32.0) -Grip strength: 50% returned to normal at 1 yr and 54% at 3 yrs -Chair stands/min improved: Baseline (25.6), 12 mos (35.0), 24 mos (39.0), 36 mos (40.7); p=0.002 -Chair stands: 44% returned to normal at 1 yr and 64% at 3 yrs	-Older age (time x age interaction, p=0.01) and male gender (time x gender interaction, p=0.002) were associated with slower recovery in timed chair stands -Age and gender were not associated with recovery for other functional status measures
Verdonck-de Leeuw 201457/10	Single center observational cohort (Netherlands)	HNSCC, all stages (curative only)	164	Median age 59 (range 40-84)	Chemoradiation (generally cisplatin)	EORTC QLQ-C30 PF	Pretx (1 wk before tx); 6 wks; 6, 12, 18, 24 mos post-RT	Change score	-EORTC QLQ-C30 worsened in the first 6 wks, then improved in survivors -EORTC QLQ-C30 worsened in non-survivors	-Comorbidity (p=0.03) and non-survivors were associated with lower EORTC QLQ-C30 PF over time
Watters 200358/10	Single center observational cohort (Canada)	Breast, all stages	65 (45 young, 25 old)	Old (65+): mean age 70 (SD 5, range 65-80) Young (>65): mean age 55 (SD 6, range 31-64)	5-FU, doxorubicin, cyclophosphamide	EORTC QLQ-C30 PF, SF-36 PF, KPS, handgrip strength	Pretx; prior to cycle 3; 3 wks post-cycle 6; 6 mos, 12 mos	Change score	-EORTC QLQ-C30 and SF-36 PF were lower at completion of chemo (p<0.01 and p<0.05, respectively) -EORTC QLQ-C30 and SF-36 PF were similar from baseline to follow-up -KPS declined significantly by completion of chemo (92 +/− 6 vs. 85 +/− 11, p<0.001) -KPS did not differ from baseline to follow-up -No change in handgrip strength	-Younger age was associated with greater decline in EORTC QLQ-C30 PF (p<0.05) -Age was not associated with changes in SF-36 PF
Williamson 201859/10	Single center observational cohort (US)	Lung, all stages	101	Mean age 64.5 (SD 11.6)	Chemo, immunotherapy, targeted therapy, combination	FACT-L TOI (physical/functional well-being)	Baseline (study entry), 6 wks, 12 wks	Change score	-Baseline: 51.37 −6 wks: 33.17 −12 wks: 44.55	-Lower baseline physical/functional well-being (p<0.001), being unmarried (p=0.017), non-Hispanic White race (p=0.004), higher internalized stigma (p=0.045) were associated with lower physical/functional well-being at 6 wks -Lower baseline physical/functional well-being (p<0.001) was associated with lower physical/functional well-being at 12 wks -Age, sex, education, smoking history, months since diagnosis, cancer stage/type, prior surgery, prior chemotherapy, and constrained disclosure (avoidance of or discomfort about disclosing one’s cancer status to others) were not associated with physical/functional well-being at 6 and 12 weeks
Yang 201860/10	Single center observational cohort (Taiwan)	NSCLC, stage IIIB-IV	344	Gefitinib: mean age 63.7 (SD 11.2); erlotinib: mean age 61.9 (SD 12.8); afatinib: mean age 60.8 (SD 10.2)	Gefitinib, erlotinib, afatinib	WHOQOL-BREF physical, mobility, daily activities	Baseline; q2-4 wks during tx up to 25 mos (no specific time point)	Change score	-Physical, mobility, and daily activities scores were lower in the afatinib arm	-ECOG PS 2-4 (vs 0-1) was associated with worse scores on physical, mobility, and daily activities (p<0.001) -EGFR exon 19 deletion was associated with worse scores on physical (p<0.05), mobility (p<0.05), and daily activities (p<0.01) -Brain metastasis was associated with worse scores on mobility (p<0.05) -Disease progression was associated with worse scores on physical, mobility, and daily activities (p<0.001) -Afatinib (vs gefitinib) was associated with worse scores on physical (p<0.05), mobility (p<0.01), and daily activities (p<0.01) -Sex, education, employment, marital status, comorbidities, and recurrence were not associated with any decline

Abbreviations: 2MWT, two-minute walk test; 6MWT, six-minute walk test; 5-FU, fluorouracil; AC, cyclophosphamide/doxorubicin; AML, acute myeloid leukemia; chemo, chemotherapy; CLAS, Cancer Linear Analogue Scale; CMF, cyclophosphamide/methotrexate/fluorouracil; 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; FACT-L TOI, Functional Assessment of Cancer Therapy-Lung Trial Outcome Index;GI, gastrointestinal; HNSCC, head and neck squamous cell carcinoma; IADL, instrumental activities of daily living; MCID, minimal clinically important difference; mo, month; mos, months; NHL, non-Hodgkin lymphoma; PCS, Physical Component Summary; PF, physical functioning; posttx, posttreatment; pretx, pretreatment; PS, performance status; QOL-ACD, Quality of Life Questionnaire for Cancer Patients Treated with Anti-Cancer Drugs; RCT, randomized controlled trial; NSCLC, non-small cell lung cancer; SCLC, small cell lung cancer; SCT, stem cell transplant; SD, standard deviation; SF, short-form; vs, versus; wk, week; wks, weeks; tx; treatment; WHO, World Health Organization; WHOQOL-BREF, World Health Organization Quality-of-Life Brief; 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.