Aging and CancerArash Naeim, MD PHDDirector, Geriatric-Oncology Program“If you’re not a pediatric oncologist,you’re a geriatric oncologist.”Saying in Oncology, source unknownA 75 year old womanA 75 year old womanIn a wheelchairWould you send her for a screening mammogram?If she had triple negative lymph node + breastcancer would you send to a medical oncologist foradjuvant chemotherapy post-operatively ?Would you send her for ascreening mammogram?If she had triple negative lymph node+ breast cancer would you send to amedical oncologist for adjuvantchemotherapy post-operatively ?A 75 year old womanJust to and from clinicA 75 year old womanFatigue and weaknessIn a wheelchairAll the timeIn a wheelchairArthritisWould you send her for ascreening mammogram?Would you send her for ascreening mammogram?
A 75 year old womanIn a wheelchair due to arthritiswith a myocardial infarction last yrA 75 year old womanIn a wheelchair due to arthritiswith a myocardial infarction last yrDiabetesStrokeModerate Chronic Renal InsufficiencyHypertensionWould you send her for ascreening mammogram?Would you send her for ascreening mammogram?A 75 year old womanIn a wheelchair due to arthritiswith a myocardial infarction last yrwith diabetes, HTN, and mod CRIwith Alzheimer’s dementiaA 75 year old womanIn a wheelchair due to arthritiswith a myocardial infarction last yrwith diabetes, HTN, and mod CRIwith Alzheimer’s dementiaMild to ModerateSevereWould you send her for ascreening mammogram?Would you send her for ascreening mammogram?A 75 year old womanIn a wheelchair due to arthritiswith a myocardial infarction last yrwith diabetes, HTN, and mod CRIwith mild Alzheimer’s dementiawith a strong preferenceWould you send her for ascreening mammogram?If she had triple negative lymph node+ breast cancer would you send to amedical oncologist for adjuvantchemotherapy post-operatively ?
ATHENA Breast NetworkUCSF, UCLA, UCSD,UCI, UCD + UCBPI: Esserman, LauraUCLA Site PI: Naeim, ArashGoalFollow a cohort of 120,000 womenwho present for a screening mammogramScreening in the Older IndividualsUsing the Vulnerable Elders Survey (VES-13)and Comorbidity to Assess Life ExpectancyWhat age represent aging?The BasicsTraditional ViewWhat is geriatric oncology?PreventionScreening• No one precise definition of a ‘geriatric’patient; commonly 65 or 70 used• Among geriatricians/gerontologists, 65-74 are‘young old’, 75-84 are ‘medium old’, and 85+are ‘oldest old’• Overall it is clear that aging has led to anincreased focus on cancer in older adultsEpidemiologyEnd of LifeCancer inolder adultsDiagnosisPrognosisQualityof LifeTreatment
Geriatric ParadigmPhysiology/PharmacologyClinical trialparticipationAge biasComp.GeriatricAssessmentCancer inolder adultsLong-termcareFrailtyComorbidityFunctionalstatusNumber of Persons 65 and Older (millions)807060504030201001900 1940 1980 2000 2030YearU.S Census BureauWorld Statistics: Age 65 and OlderCancer and Aging35%3025201510501950 2000 2030YearWorld Health ReportCases/100,00025002000150010005000CancerIncidenceCancerMortality>65
Do We Address the Questions that PatientsWant to Know?Doctor, if I take the therapy…‣ will I be hospitalized?‣ will I be functionally impaired?‣ will I be cognitively impaired?‣ what does my family need to prepare for?‣ what is the quality of my survival?Will I become frail?Projected life expectancy (years)Age now Life Expectancy Age of Death65 17.7 82.770 14.3 84.375 11.2 86.280 8.5 88.585 6.3 91.390 4.5 94.595 3.3 98.3100 2.5 102.5National Vital Statistics ReportComorbidityDefinition:ComorbidityConcurrent, independent health conditionwhich may be a predictor of survival andresource requirementsKey questions:1. Is the patient going to die from cancer oranother medical problem?2. Will another medical problem limit theability to tolerate treatment?54.543.532.521.510.50Comorbidity By Age55-64 65-74 75+55-6465-7475+Age, comorbidity & life expectancy• Synergistic interaction between age &comorbidity (e.g. as measured by Index of Co-Existent Disease, ICED )Age ICED 0 ICED 1 ICED 2 ICED 365 12.5 y 10.7 y 7.1 y 2.3 y70 9.8 y 8.3 y 5.4 y 1.6 y75 7.5 y 6.3 y 3.9 y 1.1 yYancik R. Cancer 1998 82:2123-2134Albertsen JAMA 1995; 274:626
Major comorbid conditions in oldercancer patientsConditionPercentHypertension 42.9Heart disease 39.1Arthritis 34.9Gastrointestinal problems 31.0Anemia 22.6Eye Problems 19.0Urinary Tract 18.0Previous cancer 15.4Gallbladder problem 14.9COPD 14.5Diabetes 12.8Yancik Cancer 1997; 80:1273Impact of comorbidity• ↑ risk of short-term mortality andcomplications after surgery/radiation• ↑ risk of complications after chemotherapy• ↓ overall survival• ↑ likelihood of dying from other causesComorbidconditionsLess treatmentSelected(sub-optimal?)BiasPooroutcomeComorbidity Decreased Survivalin Patients with Lung Cancer302520Weeks15105Median Survival Time0No Comorbidities 1 or 2 > 2Charlson ScoreHigher comorbidity score worse survivalFrasci et al, J Clin Oncol, 2000Increased Comorbidity Correlates withCancer Treatment Discontinuation100%90%80%70%60%50%40%30%20%10%0%Discontinuation of Treatment0 to 2 >2Charlson ScoreHigher comorbidity score more likely to discontinue treatmentFrasci et al, J Clin Oncol, 2000Adjuvant Therapy
To Treat or Not: PCPsTo Treat or Not: OncologistsATHENA Breast NetworkUCSF, UCLA, UCSD,UCI, UCD + UCBPI: Esserman, LauraUCLA Site PI: Naeim, ArashGoalFollow a cohort of 5,000 womendiagnosed with breast cancerAppropriateness of Adjuvant Therapy in OlderWomen with High Comorbidity BurdenIdentify women for whom adjuvant treatmentmay not be beneficialFrailtyThe Oncologist’s Perspective of Frailty
ECOG Performance StatusThe Geriatrician’s Perspective of FrailtyGeriatrician’s Assessment of FunctionActivities of Daily Living (ADLs)Basic self-care skillsDressingBathingToiletingTransferContinenceEatingGeriatrician’s Assessment of FunctionInstrumental Activities of Daily LivingHigher order functionShoppingHousekeepingTransportationLaundryTelephoneFinancesMedicationsDifficulty with ADLs and IADLsby Age% with difficulty6050403020100ADL problemIADL Problem65-7470-7475-7980-8485+
Assistance with IADLs Worse Survivalin Patients with Lung Cancer‣Multicenter Italian Lung Cancer in the Elderly StudyHow do we apply geriatric principles toolder adults with cancer?‣Advanced non-small cell lung cancer (Stage IV or IIIB)‣566 patients‣Age 70 and older‣Association between IADL assistance and survivalMaione et al, J Clin Oncol, 2005Assistance with IADLs Worse Survivalin Patients with Lung CancerDecreased Functional Status Poorer Survival in Patients with AMLCategories of IADLs:‣63 patients with newly diagnosed AML‣ Better:Score of 100%‣ Intermediate:Score of 51-99%‣ Worse:Score of 0-50%IntermediateWorseBetter36Median 24Survival(Months)12P
Older Cancer Survivors Need MoreAssistance with ADLsOlder Cancer Survivors…‣Were less likely to report excellent or good health (P
California Breast CancerResearch Program Idea GrantIs our approach to older cancerpatient’s evidence-based?Limited oncology evidence baseSWOG Trials• Poor recruitment of older adults into clinicaltrials• Limited # of older adults even in many largetrials to facilitate subgroup analyses• Highly selected older adults in clinical trials(limited comorbidity, not disabled/frail, cognitivelyintact)Hutchins LF et al, 1999ECOG TrialsWho is placed on Clinical Trials?Lewis JH et al, 2003
Clinical Trials in the ElderlyBarriersClinical Trial Design Issues• Age versus Frailty• Dedicated Trial versus Subgroup Analysis• Interest from Pharmaceutical Companies• Outcomes (Traditional versus Novel)GI-04 : Phase II frontline oral chemo + IVtargeted agent in frail and elderly patientswith metastatic colorectal cancerGeriatric-Hematology
Other Areas of Research• Symptom Clusters and Management• Clinical Trials of Supportive Agents• Comparative Effectiveness ResearchIncreasing Recognition• Hartford Foundation• Sub-Specialty Societies (ASCO, ASH,AGS, ASP)• NIH (NCI and NIA) – P20, U01, R01