Nonclinical factors associated with premature termination of adjuvant chemotherapy for stage I-III breast cancer

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Nnclinical factrs assciated with premature terminatin f adjuvant chemtherapy fr stage I-III breast cancer Xia-Cheng Wu, Trevr Thmpsn, Meichin Hsieh, Meijia Zhu, Patricia Andrews, Michelle Lch, Timthy Styles, Vivien W. Chen 2015 NAACCR Annual Cnference Charltte, Nrth Carlina June 18, 2015 Backgrund Clinical trials and chrt studies have indicated that adjuvant chemtherapy decreases cancer recurrence and imprves survival significantly fr early stage breast cancer patients. Numerus studies examined disparities in disseminatin f guidelines-recmmended chemtherapy and factrs assciated with nn-guidelines cncrdant care 1

Backgrund It has been reprted that early terminatin f adjuvant chemtherapy has an adverse impact n prgnsis f breast cancer (Hershman D, 2005). Ppulatin-based patterns f care studies have nt examined early terminatin f chemtherapy due t difficulties in cllecting such data. CDC-funded Cmparative Effectiveness f Research (CER) prject cllected detailed infrmatin n chemtherapy including cmpletin status. Objectives Examine the assciatin f nn-clinical factrs with early terminatin f adjuvant chemtherapy amng stage I-III breast cancer patients. 2

Methds Data surces: CDC-funded Cmparative Effectiveness Research (CER) prject including data frm seven state cancer registries (CO, FL, ID, LA, NC, NH, and RI). 3 CER registries were excluded due t high prprtin f missing infrmatin n chem cmpletin status. Methds Medical recrd re-abstractin fr infrmatin available up t 12 mnths after diagnsis: hspitals nn-hspital settings, including - free-standing ambulatry centers - radiatin facilities - physician practice grups - medical nclgists 3

Methds Eligibility criteria Wmen at all ages Residents in the 7 states at diagnsis Stage I-III breast cancer (C50.0-50.9, excluded 9050-9055, 9140, 9590-9992) diagnsed in 2011. Micrscpically cnfirmed N autpsy r death-certificate-nly cases Received chemtherapy Have infrmatin n chem cmpletin status Methds Nn-clinical (sci-demgraphic) variables Age: <40, 40-49, 50-64, 65-69, 70-79, 80/+ Race/ethnicity: NHW, NHB, API, Hispanics, Others, Unk Insurance: Private, Medicare/ther public, Medicaid, Nne, Unknwn Census-tract level pverty: lw<20%, high >20% f peple under federal pverty level. Census-tract level educatin: lw<25%, high >25% f peple 25 years and lder with at least a high schl educatin. 4

Methds Clinical variables: Reginal lymph nde: n, micr-metastasis (<2 mm), N1/N2/N3 Tumr size (cm): <0.5, 0.6-<1.0, 1.0-2.9, >3.0, unknwn Histlgy: Ductal/lbular/mixed, Tubular/Cllid, thers Grade: well, mderate, prly/undifferentiated, unknwn Hrmne receptr: ER+ r PR+, ER- & PR-, unknwn Cmrbidity: nne, mild, mderate/severe Primary treatment: n surgery, mastectmy, lumpectmy + radiatin, lumpectmy nly, unknwn Methds Cmrbid cnditins: Nne: N dcumentatin f Charlsn cnditin Mild: ne r mre Charlsn cnditins with a weight f 1 and n cnditin with a weight > 2 Mderate/Severe: One r mre Charlsn cnditins with a weight > 2 Diabetes with sequelae (weight=2) Hemiplegia/Paraplegia (weight=2) Renal disease (weight=2) Mderate/severe liver disease (weight=3) AIDS (weight=6) 5

Nt received chem: 11,419 (56%) Chem extended beynd 12 mnths after diagnsis: 613 (7%) 20,288 stage I-III cases N=8,412 N=6,606 Unknwn if chem given: 457 (2%) Missing chem cmpletin status: 1,193 (14%) Missing independent variables fr mdels: 699 (11%) N=5,907 Methds Univariate analysis Multivariate lgistic regressin Outcme: Early terminatin f Chem (Yes, N) Imputatin: Data were imputed using predictive mean matching with the argimpute functin in R. Using age, race/ethnicity, educatin, pverty, insurance, residence (urban, rural, mixed), state, 1st primary (yes/n), grade, ndes, histlgy type, tumr size, ER/PR, hrmnes, surgery type, the individual cmrbid cnditins*, weight, height, smking status, and chem cmpletin status t predict missing value. SAS prgrams. 6

Results Overall, 23% f the patients terminated chem early. Reasn chem nt cmpleted Health issues/cmplicatins 63.3% Deceased 1.7% Patient/family chice 21.7% Cytpenia 2.3% Other reasns 11.0% Ttal 100% Results All cases (N=6,606) Early chem terminatin (N=1,543) Age at diagnsis P<0.0001 <40 8.7% 21.0% 40-49 24.0% 18.3% 50-64 45.4% 22.4% 65-69 11.1% 25.7% 70-79 9.3% 37.1% 80/+ 1.5% 45.9% 7

Results All cases (N=6,606) Early chem terminatin (N=1,543) Race/ethnicity P=0.4409 White 69.5% 22.7% Black 18.3% 24.4% API 1.6% 25.2% Hispanic 9.7% 25.6% Other 0.9% 22.8% Unknwn 0.2% 33.3% Results Insurance All cases (N=6,606) Early chem terminatin (N=1,543) P<0.0001 Private 63.7% 20.0% Medicare/Other Public 17.1% 31.6% Medicaid 12.8% 28.6% Nne 4.5% 26.4% Unknwn 2.0% 18.5% 8

Results All cases (N=6,606) Early chem terminatin (N=1,543) Census tract pverty P=0.2160 Lw (<20%) 86.7% 23.1% High (>20%) 12.6% 25.0% Unknwn 0.7% 26.5% Census tract educatin P=0.0184 High (<25%) 84.0% 22.7% Lw (>25%) 15.3% 26.6% Unknwn 0.7% 26.7% Multivariate Lgistic Regressin Mdel Outcme: Early chem terminatin (Yes vs. N) Mdel 1 Mdel 2 Mdel 3 Race White 1.00 1.00 1.00 Black 1.21 (1.03-1.42) 1.12 (0.96-1.32) 1.06 (0.89-1.28) API 1.29 (0.79-2.09) 1.30 (0.80-2.12) 1.24 (0.74-2.03) Hispanic 1.21 (0.98-1.49) 1.18 (0.96-1.46) 0.76 (0.60-0.97) Other 1.16 (0.60-2.24) 1.13 (0.58-2.20) 0.85 (0.43-1.69) Mdel 1: adjusted fr age nly Mdel 2: adjusted fr age and clinical factrs (cmrbidity, lymph nde, tumr size, histlgy type, grade, surgery and radiatin). Mdel 3: adjusted fr age, clinical factrs, and demgraphic factrs (race/ethnicity, insurance, pverty, educatin, urban/rural, and registry). 9

Multivariate Lgistic Regressin Mdel Outcme: Early chem terminatin (Yes vs. N) Mdel 1 Mdel 2 Mdel 3 Insurance Private 1.00 1.00 1.00 Medicare/ Other public 1.40 (1.16-1.70) 1.38 (1.14-1.67) 1.44 (1.18-1.75) Medicaid 1.62 (1.35-1.93) 1.52 (1.27-1.82) 1.54 (1.27-1.86) Nne 1.60 (1.21-2.12) 1.49 (1.12-1.98) 1.48 (1.10-1.98) Mdel 1: adjusted fr age nly Mdel 2: adjusted fr age and clinical factrs (cmrbidity, lymph nde, tumr size, histlgy type, grade, surgery and radiatin). Mdel 3: adjusted fr age, clinical factrs, and demgraphic factrs (race/ethnicity, insurance, pverty, educatin, urban/rural, and registry. Multivariate Lgistic Regressin Mdel Outcme: Early chem terminatin (Yes vs. N) Mdel 1 Mdel 2 Mdel 3 Pverty Lw (<20%) 1.00 1.00 1.00 High (>20%) 1.09 (0.91-1.31) 1.05 (0.87-1.26) 0.97 (0.78-1.20) Educatin High (<25%) 1.00 1.00 1.00 Lw (>25%) 1.22 (1.04-1.44) 1.18 (1.00-1.39) 1.13 (0.93-1.37) Mdel 1: adjusted fr age nly Mdel 2: adjusted fr age and clinical factrs (cmrbidity, lymph nde, tumr size, histlgy type, grade, surgery and radiatin). Mdel 3: adjusted fr age, clinical factrs, and demgraphic factrs (race/ethnicity, insurance, pverty, educatin, urban/rural, and registry. 10

Cmrbidities Multivariate Lgistic Regressin Mdels Outcme: Early chem terminatin (Yes vs. N) Mdel 1 Mdel 2 Mdel 3 Nne 1.00 1.00 1.00 Mild 1.08 (0.91-1.27) 1.07 (0.91-1.27) 1.11 (0.93-1.33) Mderate/ severe 2.27 (1.25-4.11) 2.14 (1.17-3.91) 1.90 (1.02-3.54) Mdel 1: adjusted fr age nly Mdel 2: adjusted fr age and clinical factrs (cmrbidity, lymph nde, tumr size, histlgy type, grade, surgery and radiatin). Mdel 3: adjusted fr age, clinical factrs, and demgraphic factrs (race/ethnicity, insurance, pverty, educatin, urban/rural, and registry. Multivariate Lgistic Regressin Mdel Outcme: Early chem terminatin (Yes vs. N) Primary treatment Mdel 1 Mdel 2 Mdel 3 Mastectmy 1.00 1.00 1.00 Lumpectmy + radiatin 0.99 (0.86-1.12) 1.05 (0.91-1.21) 1.02 (0.89-1.18) Lumpectmy w radiatin 1.62 (1.26-2.07) 1.73 (1.34-2.22) 1.85 (1.43-2.40) N surgery 3.07 (2.12-4.44) 2.81 (1.94-4.08) 2.77 (1.88-4.07) Mdel 1: adjusted fr age nly Mdel 2: adjusted fr age and clinical factrs (cmrbidity, lymph nde, tumr size, histlgy type, grade). Mdel 3: adjusted fr age, clinical factrs, and demgraphic factrs (race/ethnicity, insurance, pverty, educatin, urban/rural, and registry). 11

Cnclusins/Discussins Medicaid r Medicare/ther public insurance is a significant predictr fr early terminatin f chem after adjusting fr age, clinical, and ther sci-demgraphic factrs. Wells JS, et al (2015) reprted patients nt cvered by private insurance were mre likely t cmplete less than 100% f chemtherapy. Cnsistent with recent studies (Andic F 2010, Lipscmb J, 2012, Wells JS, 2015), race/ethnicity is a nt significant predictr fr early terminatin f chem after the adjustment. Pverty and educatin are nt significant predictrs fr early terminatin f chem after the adjustment. Cnclusins Mderate/severe cmrbidity is a significant predictr fr early terminatin f chem. N guideline primary treatment (lumpectmy withut radiatin therapy r n surgery) significantly predicts early terminatin f chem. 12

Strength: The first ppulatin-based study n early chem terminatin Large sample size Include all majr race/ethnicity categries Data are relatively current (2011 diagnsis) Limitatin: 15% f cases unknwn chem cmpletin status Cmrbidity cllectin was nt standardized Only examined early terminatin (yes, n). Nt examined adherence, which includes Delayed chem, missed and cancelled appintments Reduced dse Underlying cause fr the assciatin f insurance with early chem terminatin is unknwn. Acknwledgement CDC-funded CER Prject CDC-NPCR specialized cancer registries NCI-SEER Prgram All frm CDC and participating registries wh were invlved in this study. 13

Thank Yu! Cntact infrmatin xwu@lsuhsc.edu (504) 568-5757 14