Quality of life and its health-relations

Definitions

Definitions

Subjective Multi-dimensional

DynamicPhysicalFunctioning Social

FunctioningEmotional

Functioning

Outcome Assessment

Disease level(lab data)

(clinical data)

Patient level(lab data)

(clinical data)

Why assess health-related quality of life in cancer patients

• Consumerism and outcome research drive

• Helps design new approaches/monitor effectiveness

• Improve clinicians’ knowledge of patients’ subjective experience

• Health economic evaluation

• Reliable HRQOL outcome can help give a comprehensive picture of the treatment outcome supporting decision-making policy

Who can best assess QOL

• Doctor and nurses consistently underestimate patients’ levels of QOL

• Patients are the best judge of their subjective well-being

BUT• Difficult scientific methodology• Requires good doctor-patient communication• Requires collaboration with other experts• Resource intensive (assistants, nurses)

How should we assess QOL

• EORTC QLQ-C30 Questionnaire• FACT-G – Functional Assessment of Cancer

Therapy• FLIC – Functional Living Index for Cancer• Rotterdam Symptom Checklist

EORTC-QLQ C30

Minimum important difference (MID)

• The smallest difference in score in the outcome of interest

• Which patients perceive as beneficial• And which would mandate, in the absence of

troublesome side effects and excessive cost, a change in the patient’s management

MID

• 10 point difference on a 0-100 scale, EORTC’s QLQ suite, widely used as threshold for clinically important different

MID

Comparison Improved Deteriorated

Ringash et al. Other patients 4.4 8.3

Cella et al., 2002Own rating of change over

time5.5 9.9

Cella et al., 1997 Change in Karnofsky PS 5.4 6.8

Measuring Quality of Life in Routine Oncology Practice Improves Communication and Patient Well-Being

• Velikova et al. J Clin Oncol 2004; 22: 714-724.

The intervention

1.QOL evaluated by EORTC QLQ-C30 before seeing the doctor

2.QOL graphs attached to medical notes; Physicians review QOL results

3.After each intervention the physicians filled visit-specific checklist

4.Patients imopression on communucation was recorded

Discussion

• Regular QOL measurements has positive impact on:– Physician-patient communication– Patient well-being• Symptom control and emotional well-being

– Improvement in patient well-being was associated with explicit use of QOL information during consultations

Opinions

• Participating patient:– I felt that people were still interested in me.

People were still wanting to know. I wasn’t written off altogether.

• Participating physician:– I actually think that’s the most powerful thing.

Baseline quality of life as prognostic indicator of survival: a meta-analysis of individual patient data from

EORTC clinical trials.

• Quinten C et al. Lancet Oncology, 2009; 10: 865-71.

Trial Data:30 EORTC Trials11 cancer sites10.108 patientsPre-intervanetion QOL measures

ResultsFinal Model HR MA Estimate HR Inclusion variable

(%)

WHO=0-1 vs. WHO=2-3 1.07 1.07 100

Age<60 vs. Age>60 1.17 1.17 100

Non-meta vs. Meta 1.70 1.70 100

Male vs. Female 0.74 0.74 100

Physical functioning 0.94 0.95 100

Pain 1.04 1.04 99.7

Appentite Loss 1.05 1.05 100

Conclusion

• QOL parameters: pain, physical functioning, appetite loss provide prognostic information beyond clinical measures.

• This effect holds across the different diseases sites and therefore taking into account QOL parameters can improve survival prediction of cancer patients

Genetics and QOL

• The heritability of self-reported health• 4.638 male-male twins• Regression model• Genetic variables accounted for 33% of the

variability in self-reported health

QOLenomics?

• The study of how inherited genetic variations affect aspects of patient quality of life as well as the use of that knowledge in treatment discovery and development

• Could genetic variation explain why one person experiences profound deficits in QOL while another person reports no QOL deficits from the same disease?

Preliminary Evidence of Relationship Between Genetic Markers and Oncology Patient QOL Prior to Treatment

• JA Sloan et al. Mayo Clinic Camprehensive Cancer Center

• Background– Genetic predispositions exist for depression, suicide,

alcoholism, smoking and other psychological variables• 5-HT receptor• APOE epsilon 4 allele• Androgen-regulator genes

Study plan

• 22 candidate genes variants in 11 genes ebaluated

• 494 patients with both genetic samples and QOL data at baseline

Results

• DPYD*5 was significantly associated with patient-reported fatigue (p=0.008)

• The homozygous variant was associated with lower fatigue scores (worse QOL)

DPYD

• DPYD gene:– Involved in pyrimidine base degradation– Catalyzes the reduction of uracil and thymine– Only endogenous source of neurotransmitter B-

alanine• DPYD*5/*6 polymorphism:– Could be in linkage disequilibrium with another

genetic variant that directly affects cellular metabolism, and thus QOL.

Implications

• Identify cancer patients with genetic predisposition for deficits in QOL

• Effective pharmacologic and psychosocial interventions exist for QOL

• Genetically-targeted, individualized treatments for QOL might be possible