1. Prevalence, Correlates, & Outcomes of Chemotherapy for Patients with End-Stage Gastrointestinal Cancers Holly G. Prigerson, PhD Renee C. Maciejewski, BS Manish A. Shah, MD Yuhua Bao, PhD Paul K. Maciejewski, PhD Center for Research on End-of-Life Care Weill Cornell Medicine

2. Learning Objectives After this presentation, participants should know the:  prevalence  patient profile  outcomes Presented by: Holly G. Prigerson, Ph.D associated with chemotherapy use for GI cancer patients who are nearing death

3. Presentation Outline This talk will present data on the: a.frequency b.correlates c.harms & benefits of chemotherapy use in patients in their final months of life Presented by: Holly G. Prigerson, Ph.D.

4. Frequency of chemotherapy use in GI cancer patients near death Administration codes from SEER-Medicare data reveal that: Stage IV pancreatic cancer patients diagnosed 2006 – 2011 who died within a year of their diagnosis (total N=7998): –35% chemotherapy Stage IV pancreatic cancer patients diagnosed in 2011 and then died in 2012 (total N=1270): –37% chemotherapy Presented by: Holly G. Prigerson, PhD

5. Frequency of chemotherapy use in GI cancer patients near death From Coping with Cancer NCI R01 data: Sites: Yale Cancer Center, Dana-Farber/BWH, MGH, University of Texas Southwestern (Parkland, Simmons), Pomona Valley Hospital, New Hampshire Oncology Hematology, Weill Cornell/Meyer, University of New Mexico, Massey, Memorial Sloan-Kettering Cancer Centers Patients: GI cancer patients – distant mets and refractory to at least 1 line of chemotherapy a median of 4 months from death CwC I (2002-2008): 50% patients using chemotherapy at baseline assessment Presented by: Holly G. Prigerson, Ph.D

6. From Coping with Cancer NCI R01 CwC II data (2010-2015): The question “Are you currently receiving chemotherapy?” The answer: pre-restaging scan = 90% receiving chemotherapy post-restaging scan = 81% receiving chemotherapy In the medical chart abstraction following restaging scan: 86% current chemotherapy use Across pre, post, and the med chart: 94%! receive chemotherapy Presented by: Holly G. Prigerson, Ph.D

7. All participants (n=386) Before propensity weighted adjustment After propensity weighted adjustment Chemotherapy P- value Chemotherapy P-value Yes (n=216) No (n=170) Yes (n=216) No (n=170) Age (yrs)58.4 (12.5)56.4 (12.3)61.0 (12.5)<0.00157.9 (11.9)57.9 (12.2)>0.9 Male215 (56)119 (55)96 (56)0.8(55.8) >0.9 Married236 (61)142 (66)94 (55)0.04(58.0) 0.8 Insured238 (62)145 (67)93 (55)0.02(55.9)(55.8)0.8 Mean (SD) years of education 12.6 (4.0)13.3 (3.9)11.6 (4.0)<0.00111.9 (4.1)11.9 (4.2)>0.9 Race/ethnicity: 0.10.7 White251 (65)147 (68)104 (61)(58.7) Black70 (18)36 (17)34 (20)(22.1) Hispanic57 (15)26 (12)31 (18)(18.4) Asian5 (1)5 (2)0 (0)(0.7)(0.0) Religion: 0.5>0.9 Catholic141 (36)76 (35)65 (38)(34.6) Protestant68 (18)42 (19)26 (15)(16.0) Jewish18 (5)14 (6)4 (2)(3.4) Muslim5 (1)3 (1)2 (1)(0.7) No religion17 (4)8 (4)9 (5)(6.1)(5.0) Pentecostal9 (2)6 (3)3 (2)(3.7)(1.7) Baptist58 (15)29 (13)29 (17)(17.0)(19.5) Participants’ characteristics by chemotherapy at study enrollment Those getting chemo are:  younger  married  insured  better educated

8. All participants (n=386) Before propensity weighted adjustment Chemotherapy P value Yes (n=216)No (n=170) Participants’ characteristics by chemotherapy at study enrollment Mean (SD) performance status‡: Karnofsky score 64.8 (16.2)69.0 (14.8)59.5 (16.4)<0.001 ECOG score1.7 (0.9)1.5 (0.9)2.0 (0.9)<0.001 Charlson Comorbidity Index 8.3 (2.7)7.9 (2.3)8.8 (3.0)0.002 Mean (SD) McGill Quality of Life§: Physical functioning 5.7 (2.6)6.1 (2.4)5.3 (2.9)0.004 Symptoms5.4 (2.1)5.8 (2.0)4.9 (2.1)<0.001 Psychological:7.2 (2.5)7.6 (2.4)6.7 (2.6)0.002 Depressed7.4 (2.9)7.7 (2.7)7.0 (3.2)0.03 Worried6.9 (3.2)7.2 (3.0)6.4 (3.3)0.01 Sad7.3 (3.0)7.9 (2.7)6.4 (3.2)<0.001 Terrified7.2 (3.1)7.4 (2.8)7.0 (3.4)0.2 Support8.6 (1.6)8.6 (1.7)8.7 (1.6)0.9 Sum score of quality of life 6.8 (1.5)7.0 (1.4)6.6 (1.6)0.002 Those getting chemo:  better performance status  better QoL at baseline (when on chemo)

9. All participants (n=386) Before propensity weighted adjustment Chemotherapy P value Yes (n=216)No (n=170) Participants’ characteristics by chemotherapy at study enrollment Institution: <0.001 Yale Cancer Center 75 (19)58 (27)17 (10) Veterans Affairs CCC 19 (5)8 (4)11 (6) Parkland and Simmons Cancer Center 188 (49)106 (49)82 (48) MSKCC28 (7)26 (12)2 (1) Dana-Farber and Massachusetts General 7 (2)3 (1)4 (2) New Hampshire Oncology Hematology 67 (17)14 (6)53 (31) Cancer: 0.02 Lung85 (22)43 (20)42 (25) Pancreatic36 (9)27 (13)9 (5) Colorectal57 (15)38 (18)19 (11) Other gastrointestinal 57 (15)27 (13)30 (18) Breast42 (11)27 (13)15 (9) Other†110 (29)54 (25)56 (33) Those getting chemo are: > academic (MSKCC) < community (NHOH) cancer centers > GI cancers (75% pancreatic)

10. Presented by: Holly G. Prigerson, Ph.D Treatment preferences and planning: Wants prognostic information 269 (69)152 (70)117 (69)0.8 Life extending care over comfort care 129 (31)85 (37)44 (24)0.01 Chemotherapy to extend life by 1 week 288 (77)186 (89)102 (62)<0.001 Wants to avoid dying in ICU 161 (39)76 (33)85 (47)0.1 All participants (n=386) Before propensity weighted adjustment Chemotherapy P value Yes (n=216)No (n=170) Participants’ characteristics by chemotherapy at study enrollment Those getting chemo:  want life- prolonging>comfort care  want chemo even if prolongs life just a week

11. Presented by: Holly G. Prigerson, Ph.D Completed living will or DPA 214 (55)111 (51)103 (61)0.1 Completed DNR order 161 (42)77 (36)84 (49)<0.05 Terminal illness acknowledgment 159 (40)76 (35)83 (47)0.04 Patient-physician communication: Therapeutic alliance with physician 244 (64)131 (62)113 (67)0.3 Discussed end of life wishes with physician 162 (42)80 (37)82 (48)0.03 Coping style: Active177 (46)105 (49)72 (42)0.3 Emotional190 (49)106 (49)84 (49)>0.9 Behavioral disengagement 82 (21)31 (14)51 (30)<0.001 Mean (SD) positive religious coping 11.2 (6.4)11.3 (6.3)11.0 (6.5)0.6 All participants (n=386) Before propensity weighted adjustment Chemotherapy P value Yes (n=216)No (n=170) Those getting chemo:  are less likely to complete a DNR order & acknowledge they’re terminally ill  are less likely to discuss EOL care preferences  more engaged (less withdrawn) Participants’ characteristics by chemotherapy at study enrollment

12. Medical care in last week* Propensity weighted adjusted analysis Chemotherapy at enrollment Risk difference (95% CI) P value YesNo CPR, ventilation, or both 24 (12)4 (2)10.5 (5.0 to15.5)<0.001 Admission to intensive care unit 26 (13)15 (8)5.6 (−0.5 to 11.7)0.07 Chemotherapy12 (6)10 (5)1.1 (−3.6 to 5.7)0.7 Feeding tube for enteral nutrition 22 (12)9 (5)7.1 (1.7 to 12.5)0.01 Hospice ≤1 week96 (52)70 (38)13.6 (3.6 to 23.6)0.008 Associations between chemotherapy at study enrollment and intensity of end of life care. Outcomes of chemotherapy use

13. Title of graphic Presented by: Holly G. Prigerson, Ph.D Variable* Unadjusted analysisPropensity weighted adjusted analysis Chemotherapy at enrollment Risk difference (95% CI) Chemotherapy at enrollment Risk difference (95% CI) P value Yes (n=216)No (n=170)YesNo Place of death: Intensive care unit 24 (11)4 (2) 8.8 (4.0 to 13.6) 19 (10)7 (4)6.1 (1.1 to 11.1)0.02 Hospital54 (25)26 (15) 9.8 (1.9 to 17.8) 38 (21)32 (17)3.6 (−4.1 to 11.3)0.4 Home102 (47)112 (66) −18.4 (−8.7 to −28.2) 100 (52)122 (63)−10.8 (−1.0 to −20.6)0.03 Inpatient hospice 28 (13)19 (11) −1.8 (−4.7 to −8.4) 26 (13)22 (12)2.0 (−4.6 to 8.7)0.6 Nursing home 7 (3)9 (5) −2.0 (−6.2 to 2.1) 7 (4)9 (5)1.0 (−5.0 to 3.1)0.6 Death in preferred place 140 (65)135 (80) −12.4 (−3.6 to −21.2) 131 (68)154 (80)−9.4 (−0.8 to −18.1)0.03 Outcomes of chemotherapy use

14. Prigerson et al. JAMA Oncol. 2015 Patients’ Higher Quality of Life Near Death Stratified by Baseline Performance Status and Chemotherapy Use ECOG indicates Eastern Cooperative Oncology Group. Performance status was measured by ECOG score as follows: 1. symptomatic, ambulatory 2. symptomatic, in bed less than 50% of the time 3. symptomatic, in bed more than 50% of the time 44% 69%

15. Conclusions  Prevalence of chemotherapy in GI cancer patients within months of death is: –frequent (~ 50%) –nearly universal at academic medical centers –becoming more common Presented by: Holly G. Prigerson, Ph.D

16. Conclusions GI cancer patients with progressive metastatic disease receiving chemo are more likely to be: –younger –married –better educated – > academic cancer clinics; < community cancer clinics Presented by: Holly G. Prigerson, Ph.D

17. Conclusions GI cancer patients with progressive metastatic disease who are receiving chemo are more likely than those who do not to: –have better baseline performance status, QoL –want life-prolonging care, including chemo even if only enhancing survival by a week –lower rates of DNR order completion, terminal illness acknowledgment, & EoL discussions Presented by: Holly G. Prigerson, Ph.D

18. Conclusions GI cancer patients with progressive metastatic disease who get chemo are at risk in their last week of: – CPR – feeding tube – ICU stay and death – hospice stays of only a few days – not dying at home or in preferred place of death Presented by: Holly G. Prigerson, Ph.D

19. Conclusions GI cancer patients near death who get chemo are likely to have: –good performance status –and, therefore, have the most to lose as they are: are more likely to have poor quality of death Presented by: Holly G. Prigerson, Ph.D

20. We appreciate this opportunity to present at ASCO 2016 GI Cancers Symposium! Thank You! Presented by: Holly G. Prigerson, Ph.D

21. Chemotherapy Use, Performance Status, & Quality of Life at the End of Life Prigerson et al. JAMA Oncology 2015