This is a presentation I did at the us city of hope comprehensive cancer center in february 2011. The topic was future of screening for distress (and depression) in cancer; including an overview of recent screening findings.

1. City of Hope Grand Round
City of Hope Grand Round
The Future of Screening for Distress in Cancer
The Future of Screening for Distress in Cancer
Alex J Mitchell www.psycho-oncology.info
Department of Cancer & Molecular Medicine, Leicester Royal Infirmary
Department of Liaison Psychiatry, Leicester General Hospital
US Feb 2011
US Feb 2011

2. Depression
Three D’s
Dysfunction
Distress

3. T0. Contents
1. Why Screen?
2. Why focus on distress?
3. Screening tools (validity & acceptability)
4. New screening
5. Where to go in the future

4. T1. Why Screen?
Survivorship
‘Diagnosis as usual’

5. 5 Year Survival in US Cancers (2008 American Cancer Society, Atlanta)
100
90
80
1975-1977
70 1984-1986
1996-2004
60 Change
50
40
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20
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Annual report to the national of status of cancer 1975 – 2005 J Natl Cancer Inst 2008;100: 1672 – 1694

6. Total prevalence = 13.8raw 000'S in 2010
million
3500 Projected = 18.2million in 2020
3000
2500
2000
raw 000'S
1500
1000
500
0
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Angela B. Mariotto J Natl Cancer Inst 2011;103:117–128

7. What is the prevalence of depression?
Levine PM, Silberfarb PM, Lipowski ZJ. Mental disorders in cancer
patients. Cancer 1978;42:1385–91.
Dartmouth Medical School and the Norris Cotton Cancer Center, New Hampshire

8. Prevalence of depression in Oncology settings Plumb & Holland (1981)
Proportion meta-analysis plot [random effects]
0.7750 (0.6679, 0.8609)
Levine et al (1978) 0.5600 (0.4572, 0.6592)
Ciaramella and Poli (2001) 0.4900 (0.3886, 0.5920)
Massie et al (1979) 0.4850 (0.4303, 0.5401)
70 studies involving 10,071 individuals;14 countries. Bukberg et al (1984)
Passik et al (2001)
0.4194 (0.2951, 0.5515)
0.4167 (0.2907, 0.5512)
16.3% (95% CI = 13.9% to 19.5%) Baile et al (1992)
Morton et al (1984)
Hall et al (1999)
0.4000 (0.2570, 0.5567)
0.3958 (0.2577, 0.5473)
0.3722 (0.3139, 0.4333)
Burgess et al (2005) 0.3317 (0.2672, 0.4012)
Jenkins et al (1991) 0.3182 (0.1386, 0.5487)
Mj 15% Mn 19% Adj 20% Anx 10% Dysthymia 3%
Green et al (1998) 0.3125 (0.2417, 0.3904)
Kathol et al (1990) 0.2961 (0.2248, 0.3754)
Hosaka and Aoki (1996) 0.2800 (0.1623, 0.4249)
Fallowfield et al (1990) 0.2565 (0.2054, 0.3131)
Golden et al (1991) 0.2308 (0.1353, 0.3519)
Spiegel et al (1984) 0.2292 (0.1495, 0.3261)
Evans et al (1986) 0.2289 (0.1438, 0.3342)
Grandi et al (1987) 0.2222 (0.0641, 0.4764)
Maunsell et al (1992) 0.2146 (0.1605, 0.2772)
Berard et al (1998) 0.2100 (0.1349, 0.3029)
Joffe et al (1986) 0.1905 (0.0545, 0.4191)
Berard et al (1998) 0.1900 (0.1184, 0.2807)
Devlen et al (1987) 0.1889 (0.1141, 0.2851)
Leopold et al (1998) 0.1887 (0.0944, 0.3197)
Akizuki et al (2005) 0.1797 (0.1376, 0.2283)
Razavi et al (1990) 0.1667 (0.1189, 0.2241)
Gandubert et al (2009) 0.1597 (0.1040, 0.2300)
Alexander et al (1993) 0.1333 (0.0594, 0.2459)
Kugaya et al (1998) 0.1328 (0.0793, 0.2041)
Payne et al (1999) 0.1290 (0.0363, 0.2983)
Ibbotson et al (1994) 0.1242 (0.0776, 0.1853)
Prieto et al (2002) 0.1227 (0.0825, 0.1735)
Morasso et al (1996) 0.1121 (0.0593, 0.1877)
Desai et al (1999) [early] 0.1111 (0.0371, 0.2405)
Silberfarb et al (1980) 0.1027 (0.0587, 0.1638)
Costantini et al (1999) 0.0985 (0.0535, 0.1625)
Morasso et al (2001) 0.0985 (0.0535, 0.1625)
Ozalp et al (2008) 0.0971 (0.0576, 0.1510)
Love et al (2002) 0.0957 (0.0650, 0.1346)
Alexander et al (2010) 0.0900 (0.0542, 0.1385)
Coyne et al (2004) 0.0885 (0.0433, 0.1567)
Kawase et al (2006) 0.0851 (0.0553, 0.1240)
Walker et al (2007) 0.0831 (0.0568, 0.1165)
Grassi et al (1993) 0.0828 (0.0448, 0.1374)
Grassi et al (2009) 0.0826 (0.0385, 0.1510)
Reuter and Hart (2001) 0.0761 (0.0422, 0.1244)
Lee et al (1992) 0.0660 (0.0356, 0.1102)
Pasacreta et al (1997) 0.0633 (0.0209, 0.1416)
Sneeuw et al (1994) 0.0540 (0.0367, 0.0761)
Singer et al (2008) 0.0519 (0.0300, 0.0830)
Katz et al (2004) 0.0500 (0.0104, 0.1392)
Mehnert et al (2007) 0.0472 (0.0175, 0.1000)
Lansky et al (1985) 0.0455 (0.0291, 0.0676)
Derogatis et al (1983) 0.0372 (0.0162, 0.0720)
Hardman et al (1989) 0.0317 (0.0087, 0.0793)
Massie and Holland (1987) 0.0147 (0.0063, 0.0287)
Colon et al (1991) 0.0100 (0.0003, 0.0545)
combined 0.1730 (0.1375, 0.2116)
0.0 0.3 0.6 0.9
proportion (95% confidence interval)

9. Meta regression using the random effects model on raw porportions
Estimated slope = - 0.02 % per month (p=0.0016). Circles proportional to study size.
0.4
0.3
Proportion
0.2
0.1
0.0
0 20 40 60 80 100
Time (months)

10. Prevalence of depression in Palliative settings
24 studies involving 4007 individuals
16.9% (95% CI = 13.2% to 20.3%) Proportion meta-analysis plot [random effects]
Lloyd-Williams et al (2007) 0.30 (0.24, 0.36)
14% major 9% minor adj 15% anx 10% Jen et al (2006) 0.27 (0.19, 0.36)
Lloyd-Williams et al (2003) 0.27 (0.17, 0.39)
Payne et al (2007) 0.26 (0.19, 0.33)
Desai et al (1999) [late] 0.25 (0.10, 0.47)
Hopwood et al (1991) 0.25 (0.16, 0.36)
Lloyd-Williams et al (2001) 0.22 (0.14, 0.31)
Minagawa et al (1996) 0.20 (0.11, 0.34)
Meyer et al (2003) 0.20 (0.10, 0.35)
Breitbart et al (2000) 0.18 (0.11, 0.28)
Le Fevre et al (1999) 0.18 (0.10, 0.28)
Chochinov et al (1994) 0.17 (0.11, 0.24)
Kelly et al (2004) 0.14 (0.06, 0.26)
Wilson et al (2007) 0.13 (0.10, 0.17)
Chochinov et al (1997) 0.12 (0.08, 0.18)
Wilson et al (2004) 0.12 (0.05, 0.22)
Love et al (2004) 0.07 (0.04, 0.11)
Kadan-Lottich et al (2005) 0.07 (0.04, 0.11)
Akechi et al (2004) 0.07 (0.04, 0.11)
Maguire et al (1999) 0.05 (0.01, 0.14)
combined 0.17 (0.13, 0.21)
0.0 0.2 0.4 0.6
proportion (95% confidence interval)

11. 3500
Total prevalence Dep = 2 million in 2010
3000
Projected depression = 2.7 million in 2020
2500
Popn Orange Country
2000
raw 000'S
1500 DISTRESS
DEPRESSION
1000
500
0
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=> Who is helped?

12. 12mo Service Use (NIH, 2002)
40
34.6
35 32.7 Cancer n=4878
No Cancer n=90,737
30
25
19.1
20
% Receiving Any treatment for Mental Health
% Receiving Any treatment for Mental Health
16.1
14
15
11.7 11
8.9
10 7.7
7.2 6.5
5.7 5.7 5 6.3 6.4 6.2
5
5 3.9 3.2
2.3 1.8
0
l th
l th
ons
nt s
ti o n
s
s
75+
rs
rs
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H ea
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44
64
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Two explanations=>
No
Maria Hewitt, Julia H. Rowland Mental Health Service Use Among Adult Cancer Survivors: Analyses of the National Health Interview Survey Journal of Clinical
Oncology, Vol 20, Issue 23 (December), 2002: 4581-4590

13. Two likely reasons…..

14. 94.2%
37.4%
P Wang Harvard
8 yrs N= 9282 NCS‐R
In cancer?=>

17. 100.0
5.9
11.1
14.3
90.0 Comment: Slide illustrates diagnostic 21.4
accuracy according to score on DT 11.8
25.9
80.0 38.7 38.1
43.5 22.2 14.3
46.7
70.0 59.6
21.4
72.4
60.0 Judgement = Non-distressed
33.3 Judgement = Unclear
19.4 19.0 Judgement = Distressed
50.0
26.1
24.4 82.4
40.0
71.4
66.7
30.0
25.0 57.1
41.9 42.9 40.7
20.0 15.8
30.4 28.9
10.0
15.4
11.8
0.0
Zero One Two Three Four Five Six Seven Eight Nine Ten

18. Is there a predictor?

19. Is 10‐15 minutes enough?

20. T2. Conventional Screening Tools (1990- to date)
(1990- to date)
Razavi D, Delvaux N, Farvacques C, Robaye E. Screening for
adjustment disorders and major depressive disorders in cancer
in-patients. Br J Psychiatry 1990;156:79–83.

21. Which tool?

23. => Is it accurate?

24. HADS in Cancer
Initial Search (n= 768) Review articles (n= 16)
No data (n= 250)
No reference standard
(n= 293)
Accuracy or Validity Analyses
(n= 210) No interview standard
(n=149)
Inadequate Data
(n=11)
HADS Validity Analyses
(n=50)
Scale Sample Size Outcome
Types (cases) Measure
HADS-D Less than 30 Depression
(n=14) (n=22) (n=22)
HADS-T 30 to 100 Anxiety
(n=26) (n=20) (n=4)
HADS-A More than 100 Any Mental Ill Health
(n=10) (n=8) (n=24)

25. British Journal of Cancer (2007) 96, 868 – 874

26. Validity of HADS vs depression (DSMIV)
SE 71.6% (68.3)
SP 82.6% (85.7)
Prev 13%
PPV 38%
NPV 95%

27. Depression_HADS
1
Post-test Probability
0.9
0.8
0.7
0.6
Baseline Probability
0.5
HADSd+
0.4 HADSd-
HADS-T+
0.3
HADS-T-
HADS-A+
0.2
HASD-A-
0.1
Pre-test Probability
0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

28. Depression_all
1.00 Post-test Probability
0.90
0.80
0.70
0.60
1Q+
1Q-
0.50 Baseline Probability
DT+
DT-
2Q+
0.40 2Q-
HADSd+
HADSd-
HADS-T+
HADS-T-
0.30 BDI+
BDI-
EPDS+
EPDS-
HADS-A+
0.20 HASD-A-
0.10
Pre-test Probability
0.00
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

29. Major limitations of older screens
1. Tools are too long & scoring complex
2. Tools look for depression alone
3. No unmet needs
4. We don’t know how to handle somatic symptoms
5. What comes next?

30. Cancer Staff Psychiatrists
Ideal Method (n=226)
Effective?
Long QQ
8%
Clinical Skills Clinical Skills
Alone Alone
Algorithm 20%
17%
26%
ICD10/DSMIV
24%
ICD10/DSMIV 1,2 or 3 Sim ple
0% 1,2 or 3 Sim ple QQ
QQ 24%
Short QQ 34%
23%
Short QQ
24%
=> Symptom overlap

31. DepT
DT
23%
37%
4% 3%
3%
DT DepT
7% 1%
Non-Nil 8% 0% Nil
9%
59% 41%
4% 1%
AnxT 2% AngT
15% 2%
AnxT AngT
47% 18%

32. Problem with somatic symptoms>?

34. Comment: Slide illustrates concept of
phenomenology of depressions in
medical disease
Primary Depression Alone
Fatigue
Anorexia
Insomnia
Concentration
Secondary
Medically Unwell Alone Depression

35. Comment: Slide illustrates actual
phenomenology of depressions in
medical disease
Primary Depression
Secondary
Depression
Weight loss
Agitation
Retardation
Medically Unwell

36. Are existing criteria too complex?

37. Symptoms Clinical Significance Duration
ICD-10 Depressive Episode Requires two of the first three At least some difficulty in 2 weeks unless symptoms are
symptoms (depressed mood, loss of continuing with ordinary work unusually severe or of rapid
interest in everyday activities, and social activities onset).
reduction in energy) plus at least two
of the remaining seven symptoms
(minimum of four symptoms)
DSM-IV Major Depressive Disorder Requires five or more out of nine These symptoms cause 2 weeks
symptoms with at least at least one clinically important distress OR
from the first two (depressed mood impair work, social or personal
and loss of interest). functioning.
DSM-IV Minor Depressive Disorder Requires two to four out of nine These symptoms cause 2 weeks
symptoms with at least at least one clinically important distress OR
from the first two (depressed mood impair work, social or personal
and loss of interest). functioning.
DSM-IV Adjustment disorder Requires the development of These symptoms cause marked Acute: if the disturbance lasts
emotional or behavioral symptoms in distress that is in excess of less than 6 months
response to an identifiable stressor(s) what would be expected from Chronic: if the disturbance
occurring within 3 months of the exposure to the stressor OR lasts for 6 months
onset of the stressor(s). Once the significant impairment in social
stressor has terminated, the or occupational (academic)
symptoms do not persist for more functioning
than an additional 6 months.
DSM-IV Dysthymic disorder Requires persistently low mood two The symptoms cause clinically Requires depressed mood for
(or more) of the following six significant distress OR most of the day, for most days
symptoms: impairment in social, (by subjective account or
(1) poor appetite or overeating occupational, or other observation) for at least 2 years
(2) Insomnia or hypersomnia important areas of functioning.
(3) low energy or fatigue
(4) low self-esteem
(5) poor concentration or difficulty
making decisions
(6) feelings of hopelessness

38. 1 Depressed Mood
S Diminished interest/pleasure
e
0.9 Diminished drive
n
s Loss of energy
i Sleep disturbance
0.8
t Diminished concentration
i
0.7 v
i
t
0.6 y
0.5
0.4
Comment: Slide illustrates summary ROC
0.3 curve sensitivity/1-specficity plot for each mood
symptom
0.2
0.1
1 - Specificity
0
0
n=1523 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

41. T3. Tools II: New Screening (1998- to date)
(1998- to date)
What is available?

42. General Physical
Trained
Self-Report
Confident
Skilled
Clinician
Alone
Signs of
DS
6
Mood DISCS
Observation Screening
Visual
CDSS#10
VA-SES
SMILEY
ET/DT
YALE
Interview
HAMD-D
17 MADRAS
10

43. Distress Thermometer

44. Proportion
20.0%
Insignificant Minim al Mild Moderate Severe
18.0%
16.0%
14.0%
12.0%
10.0%
18 .4 %
8.0%
12 .9 %
6.0% 12 .3 %
11.9 %
11.2 %
4.0% 8 .1%
7.7%
7.2 %
5.0 %
2.0%
2 .8 % 2 .6 %
0.0%
Zero One Tw o Three Four Five Six Seven Eight Nine Ten
50%

45. Validity of DT vs depression (DSMIV)
SE 80%
SP 60%
PPV 32%
NPV 93%

46. DT vs DSMIV Depression
SE SP PPV NPV
DTma 80.9% 60.2% 32.8% 92.9%
DTLeicesterBW 82.4% 68.6% 28.0% 98.3%
DTLeicesterBSA 100% 59.6% 26.8% 100%
BSA = British South Asian
BW= British White

47. 1.00 Distress
Post-test Probability
0.90
0.80
0.70
0.60
DT+ [N=4]
0.50 DT+ [N=4]
Baseline Probability
1Q+ [N=4]
1Q- [N=4]
0.40 2Q+
2Q-
DT/IT+
DT/IT-
0.30
HADST+ [N=13]
HADST+ [N=13]
PDI+
0.20 PDI-
0.10
Pre-test Probability
0.00
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
Mitchell AJ. Short Screening Tools for Cancer Related Distress A Review and Diagnostic Validity Meta-analysis JNCI (2010) in press

48. Q. Problems with New Screening aka lessons from the DT
aka lessons from the DT
1. Thresholds are arbitrary
2. Link with function / qoL unknown
3. Other Emotions Ignored
4. What comes next?

49. Sample
We analysed data collected from Leicester Cancer Centre from 2008-
2010 involving 531 people approached by a research nurse and
two therapeutic radiographers.
We examined distress using the DT and daily function using the
question:
“How difficult have these problems made it for you to do your work,
take care of things at home, or get along with other people?”
“Not difficult at all =0; Somewhat Difficult =1; Very Difficult =2; and
Extremely Difficult =3”

50. Dysfunction in 531 cancer patients
60.0%
55.7%
50.0%
40.0%
34.3%
30.0%
20.0%
10.0% 7.3%
2.6%
0.0%
Unimpaired Mild Moderate Severe

51. 100% 0.02
0.00 0.00 0.00 0.00 0.00
0.03 0.04 0.03
0.01
0.06
0.08
0.09
0.07
0.17
90% 0.20
0.18 0.11
0.19
0.28
0.31
0.18
80%
0.31
0.47
70% 0.20
0.48
0.40
60%
0.50
0.40 0.53
50% 0.45
40% 0.80 0.40
0.69
0.62
30%
0.50
3=Extremely Difficult” 0.43
0.41
20%
2=Very Difficult 0.32
0.33
0.27
0.25
10% 1=Somewhat Difficult 0.20
Unimpaired
0%
Zero One Tw o Three Four Five Six Seven Eight Nine Ten

52. Distress Thermometer

53. Distress Thermometer with anchors
Extreme and incapacitating
Very Severe and very disabling
Moderately Severe and disabling
Moderate and quite disabling
Moderate and somewhat disabling
Mild-Moderate and slight disabling
Mild but not particularly disabling
Very mild and not disabling
Minimal but bearable
Minimal and not problematic
None at all

54. T4. Future of Screening
1. Help! (early slide)
2. Function
3. Mixed emotions
4. Unmet needs
5. ………..What comes next?

57. Vs DT DepT
HADS-A
AUC:
DT=0.82
DepT=0.84
AnxT=0.87 AnxT AngT
AngT=0.685

59. T5. Implementation
What to measure?
How can WE make it work?
See Acta Oncologica (2011)

61. Comment: Slide illustrates actual gain in
meta-analysis of screening
implementation in primary care

62. Pre-Post Screen - Distress
Before After
Sensitivity of 49.7% 55.8% =>+5%
Specificity of 79.3% 79.8% =>+1%
PPV was 67.3% 70.9% =>+4%
NPV was 64.1% 67.2% =>+3%
There was a non-significant trend for improve detection sensitivity (Chi² =
1.12 P = 0.29).

64. So……..the Future of Screening
Is in our hands
…..more than psychiatrists
…..more than clinicians
……patients, clinicians, researchers together

65. Thank you
ISBN 0195380193
Paperback, 416 pages
Nov 2009
Price: £39.99

66. 7. Extras
Unfiled

67. Leicester 2010 Results
DepT
23%
0.3% DepT
3% 2%
18%
Dysfunction
Distress
28% 26% 22%
Dysfunction Distress
76% 69%

68. Qualitative Aspects of Screening in Leicester
DISTRESS
43% of CNS reported the tool helped them talk with the patient
about psychosocial issues esp in those with distress
28% said it helped inform their clinical judgement
DEPRESSION
38% of occasions reported useful in improving communication.
28.6% useful for informing clinical judgement