Targeting distress during the treatment of breast cancer ... Won Lee.pdf · Targeting Distress During the Treatment of Breast Cancer Survivors Jong Won Lee, MD, PhD Asan Medical Center,

Targeting Distress During the Treatment of Breast Cancer Survivors

Jong Won Lee, MD, PhD

Asan Medical Center, Seoul, South Korea

GBCC 2015 & 4th IBCS, Jeju

Distress in people with cancer

What is distress

-the 6th vital sign in cancer care?

“Unpleasant feelings or emotions” that may cause problems

for survivors as they cope with cancer and its treatment

“Distressed” can mean

sad/hopeless/powerless/afraid/guilty/anxious/panic/discouraged/depressed/uncertain

Term “distress” rather than “anxiety and depression” was chosen because it:

Is more acceptable and less stigmatizing than

“psychiatric,” “psychosocial,” or “emotional”

Sounds “normal” and less embarrassing

Can be defined and measured by self-report

Story line

1. Paper-based experiences: 1. Background: Routine screening of distress for BC patients in the initial

treatment period

2. Analysis of distress at the time just before surgeries

3. Acceptance of referral to psychiatric professionals

4. Changes in distress status after surgery

2. Mobile-based experiences: 1. Background: Ultrashort tools for professionals to be less burdened in the

settings of conventional paper-and-pencil methods

2. Feasibility of PRO data collection via smartphone application

3. EV, SQT, and AT vs. PHQ-9

4. Future direction: DRONE (Distress Reduction in ONcology by E-health)

Story line


treatment period









Compared with “nondepressed” patients,

the odds are 3 times greater that “depressed” patients will be noncompliant with

medical treatment recommendations

MR Dimatteo. Depression is a risk factor for noncompliance with medical treatment. Arch Intern Med. 2000

http://srxawordonhealth.com/2011/10/

• Distress is associated with a number of negative outcomes: poorer adherence to treatment recommendations

Arguments about implementation of routine screening for distress

• It is practically labor intensive. • conventional screening tools • paper-and-pencil methods

• There needs to be stronger evidence for it.

• routine screening followed by referral of distressed individuals to appropriate professionals yields better control of distress?

• It seems less cost-effective.

• Distress is associated with a number of negative outcomes:

• poorer adherence to treatment recommendations • worse satisfaction with care • worse quality of life

• Distress is treatable. • Distress is common (>30%). • Distress often goes unrecognized by oncology professionals.

Against~ In favor of~

Paul B. Jacobsen. JCO. 2007

1681 consecutive patients who were admitted to AMC and received surgery with a diagnosis with breast cancer during a period between November 2012 and October 2013

1. Past history of psychological/psychiatric medication regardless of disease status (n=54) 2. Locoregional recurrence which was a candidate for surgical intervention (n=117) 3. Metastatic disease at the time of diagnosis (n=11)

1499 patients were analyzed in situ subgroup (n=148) invasive subgroup (n=1080) invasive with NST subgroup (n=271)

excluded

CES-D screening for breast cancer patients waiting for surgery

Center for Epidemiologic Studies Depression Scale 20-item questionnaire Cutoffs: 16+ (probable depressive) and 25+ (definite depressive)

In press, Psychooncology

Variables Number of patients % CES-D score

CES-D score

≥ 25

CES-D score

≥ 16

Mean SD N % N %

Total patients 1499 18.5 9.7 362 24% 850 57%

The prevalence of depression with the cutoff of 16: 57% 1.4~2.0 times higher than reported in the Korean general population

Cho MJ et al. Psychiatry Res 1998.

Kim E et al. Ann Epidemiol 2005

The prevalence can be exaggerated due to the time of CES-D, the day just before the definitive surgery


Perimenopause women were likely to be more depressed than younger or older women No evidence that younger women (<45) could be more depressed than the others

Variables Number of patients

%

CES-D score

CES-D score ≥ 25

CES-D score ≥ 16

Mean SD P N % P N % P

Total patients 1499 100% 18.5 9.7 362 24% 850 57%

Age (years) 0.016 0.107 0.084

–44 439 29% 17.4c 9.1 96 22% 230 52%

45–59 789 53% 19.0d 10.0 208 26% 465 59%

60– 271 18% 18.6c,d 9.7 58 21% 155 57%


Patients with familial cancer history (p=0.036 and p=0.037) : tend to have higher mean values of CES-D scores and higher proportions of depressive symptoms

No of family members with any malignancy

%

CES-D 16+

CES-D 25+

54% 59% 63%

23% 24%

29%

Mean %

Mean %


Patients with familial cancer history (p=0.036 and p=0.037) total mastectomy (p<0.001 and p=0.001) : tend to have higher mean values of CES-D scores and higher proportions of depressive symptoms

Mean %

Mean %

CES-D 16+

CES-D 25+


mean

Patients with familial cancer history (p=0.036 and p=0.037) total mastectomy (p<0.001 and p=0.001) advanced disease extent (p=0.005 and p=0.003) : tend to have higher mean values of CES-D scores and higher proportions of depressive symptoms

CES-D 16+

CES-D 25+


Variables

Severe, definite depression symptoms

(CES-D≥25)

Probable depression symptoms

(CES-D≥16)

Univariate Multivariate Univariate Multivariate

OR 95% CI Adjusted OR 95% CI OR 95% CI Adjusted OR 95% CI

Age at diagnosis, 45–59 years vs the others 1.29 1.01–1.64 1.28 1.00–1.64 1.21 0.99–1.49 1.20 0.97–1.48

Current smoker, yes vs no 1.75 0.97–3.15 1.58 0.87–2.88 2.29 1.21–4.34 2.01 1.05–3.85

Educational level, less tha high school vs college or more 1.34 0.98–1.84 1.38 0.99–1.92 1.27 0.96–1.68 1.21 0.90–1.63

No. of family members with any malignancy, ≥2 vs <2 or no 1.42 1.01–1.99 1.55 1.10–2.21 1.44 1.06–1.96 1.60 1.16–2.20

Sedative medication, yes vs no 1.75 1.08–2.84 1.63 0.99–2.66 2.82 1.63–4.89 2.64 1.52–4.61

Surgery type, TM vs BCO 1.34 1.01–1.77 1.20 0.89–1.62 1.53 1.18–1.98 1.43 1.09–1.89

Disease extent, invasive vs in situ 1.17 0.78–1.77 1.04 0.69–1.59 1.72 1.22–2.42 1.55 1.10–2.21

NRS pain intensity, subgroup 4 vs 1 2.64 1.53–4.55 2.45 1.40–4.29 2.07 1.31–3.27 1.78 1.11–2.84

Patients with familial cancer history (adjOR=1.60, 95% CI=1.16-2.20) total mastectomy (adjOR=1.43, 95% CI=1.09-1.89) advanced disease extent (adjOR=1.55, 95% CI=1.10-2.21) : have higher risk of having depressive symptoms

The prevalence can be exaggerated due to the time of CES-D, the day just before the definitive surgery


1681 consecutive patients who were admitted to AMC and received surgery with a diagnosis with breast cancer during a period between November 2012 and October 2013

CES-D score? day before surgery

No recommendation

N=911

<19 19 or more

N=484

N=182

N=757 ―Are you thinking of visiting stress

clinic?‖

No

Yes

Question: What makes the depressed patients (N=757) accept (N=182) the referral to the stress clinic or not?

Unknown, N=13

N=273 ―Really visited

stress clinic after discharge?‖

N=91

Yes

No

Adherence = Only 24% (182visited / 757recommended)

Among depressed patients, those who accepted the referral and visited the stress clinic had higher CES-D scores There were no associated sociodemographic factors regarding adherence to PSY recommendation

Unpublished data

Mean CES-D scores

p=0.006

Short questionnaire for QoL (including “anxiety/depression”)

5 dimensions & 3 levels

Short questionnaire for QoL (including “anxiety/depression”)

EQ-5D index score (0: worst imaginable~100: best imaginable)

Unpublished data

EQ-5D screening for breast cancer follow-up patients

Time after surgery

(month)

0~5 months

N=39

6~11 months

N=92

12~35 months

N=149

36~59 months

N=180

60 months~

N=226

n % n % n % n % n % p

Age at diagnosis

(year) <0.001

20-39 9 23.1 11 12 13 8.7 13 7.2 10 4.4

40-49 12 30.8 42 45.7 61 40.9 76 42.2 50 22.1

50-59 11 28.2 31 33.7 60 40.3 78 43.3 120 53.1

60- 7 17.9 8 8.7 15 10.1 13 7.2 46 20.4

- 686 patients who received definitive surgery at AMC from 1999 to 2012 - Screened with EQ-5D at follow-up visit (cross-sectional design), 2012 - Compared with EQ-5D scores of age-matched general population

Aims: To evaluate changes in HRQoL status of breast cancer survivors after operation and to compare that of age-matched general population (N=2,744) by using EQ-5D.

Unpublished data

EQ-5D screening for breast cancer follow-up patients EQ-5D index scores(0~1) improved up to the similar status to that of matched GP over 5 years after surgery

P=0.30 P=0.01

P<0.001 P<0.001

P<0.001

GP: General population BC: Breast cancer survivors

IF THEY SURVIVE~

Unpublished data

EQ-5D screening for breast cancer follow-up patients HRQoL scores improved up to those of general population (GP) around 2~5 years after surgery except “pain/discomfort” and “anxiety/depression” dimensions

“Problem” status in each EQ-5D category according to time after surgery

Story line


treatment period









A screening tool needs to be brief Screening for distress

• Cancer patients are frail and unwell !

• It is not easy to implement routine distress screening by conventional tools

A screening tool needs to be brief Screening for distress

• Doctors are busy and tired !

• It is labor intensive to implement routine distress screening by conventional tools

A ultrashort tool - DT

A ultrashort tool - DT

• The DT is a valid tool to detect potential distress in cancer patients

• 42 relevant studies and 14,808 patients

• At the cut-off score of 4, – Pooled sensitivity: 0.81, 95 % CI 0.79–0.82

– Pooled specificity: 0.72, 95 % CI 0.71–0.72

– AUC: 0.83

Ma X et al. The diagnostic role of a short screening tool—the distress thermometer: a meta-analysis. Supportive Care in Cancer 2014.

BRCA1

Valid Since 24 March 2014

J Med Internet Res 2014;16(5):e135

Sleep Quality Thermometer

(SQT)

Three kinds of new single-item mobile questionnaires with

visual analogue scale (VAS) format

Emotional valence

(EV)

Anxiety Thermometer

(AT)

Feasibility: How long will they use this App?

• N=30 (women with the recent diagnosis of BC)

• Mean±SD of age at diagnosis: 45.4±6.4 years (range, 36–

65 years)

• During the period of 3 months for receiving neoadjuvant

chemotherapy


Feasibility: How long will they use this App?

Everyday (twice a day) push notification!

Did you check your

journals today?


BRCA1



There were 1215 answers to 2700 requests (30 women x 90 days),

“overall compliance rate” = 45.0% ?

?

BRCA1



Median of “individual patient level reporting rates” = 41.1%

Longitudinal compliance rates

0

20

40

60

80

100

0 10 20 30 40 50 60 70 80 90 100

Patient

(%)

Time From Study Enrollment (day)

1-day

50% at 5th week

20~50%

between 6th and 10th week 10~30% therafter

The proportion of patients who self-reported at least once during each of 4 different time frames.

In prior feasibility studies with the internet, feasible thresholds for monthly- and weekly compliance were about 75%

and 60%, respectively.

0

20

40

60

80

100

0 10 20 30 40 50 60 70 80 90 100

Patient

(%)


1-day

0

20

40

60

80

100

0 10 20 30 40 50 60 70 80 90 100

Patient

(%)


1-day 1-week 2-week 4-week

Time unit Average compliance

rate 1-day 45.0%

1-week 69.7% 2-week 76.1% 4-week 82.2%

Longitudinal compliance rates

BRCA1



Why did breast cancer patients abandon to use this app?

No predictors for good compliance except “the presence

of occupation”

BRCA1



Tailored push notification may be needed

Push on 9am and 7pm everyday

BRCA1



“I just forgot” is the most common reason for missing a self-

reporting event

Easy tools for real time monitoring of distress

• Gold standard: PHQ-9Mobile version

• Novel 3 kinds of single-item VASMobile version

– EV (Emotional Valence)

– AT (Anxiety Thermometer)

– SQT (Sleep Quality Thermometer)

• Total no of the Cohort, N=70

• At about 1 month FU after initiation of neoadjuvant chemotherapy, 59

patients responded these 4 mobile questionnaires on the same

day.

Distress Reduction in ONcology by E-Health

DRONE

Receiver operating characteristic curve analysis comparing depressive symptom scores with patient health questionnaire-9 total score (the cutoff ≥ 8)

EV >4 AT >3 SQT<6 Sensitivity (%) 58.3 100.0 83.3 Specificity (%) 95.7 46.8 57.5

PPV (%) 77.8 32.4 33.3 NPV (%) 90.0 100.0 93.1

AUC (95% CI) 0.87 (0.76-0.95)

0.75 (0.62-0.85)

0.88 (0.60-0.84)

Fraction correct (%) 88.1 57.6 62.7

PUI Poor (0.45) Poor (0.32) Poor (0.28) NUI Excellent (0.86) Poor (0.47) Average (0.54) LR+ 13.7 1.9 2.0 LR- 0.4 0.0 0.3

Unpublished data

PHQ-9 ≥8 as a gold standard for depression

DRONE Distress Reduction in ONcology by eHealthcare

Summary

• At the time of breast cancer diagnosis, distress is prevalent particularly in patients with cancer family members, with advanced disease extent, or waiting for total mastectomy.

• Distress status hits its lowest level in the initial treatment period.

• Distress status continues to improve but cannot reach the status of general population by 5 year follow up.

• Targeting distress is important and further study should address the effect of early intervention on the reduction and recovery of survivors’ distress.

• Mobile based approaches can be a promising option for this purpose.

Thank you for your attention

Documents

Targeting distress during the treatment of breast cancer ... Won Lee.pdf · Targeting Distress During the Treatment of Breast Cancer Survivors Jong Won Lee, MD, PhD Asan Medical Center,