1. Solving Unknown Primary cancER (SUPER)
Established in 2014
National prospective cohort study
11 metropolitan and rural sites across Australia

2. Overall Project Aims
To establish a cohort of CUP patients with associated biospecimens, clinical, quality of life and psychosocial data
To determine the clinical management patterns when genomics test results provided to treating clinician
To establish the experiences, quality of life, psychosocial needs of patients with CUP compared to a matched sample of patients with metastatic cancer of a known primary and investigate differences between rural vs urban CUP patients

3. 1st patient recruited November 2013
SUPER – 31st March 2019
1st patient recruited November 2013
Site
Total
Peter Mac
131
Westmead 26
Nepean 15
Blacktown
Flinders 14
Geelong 29
Warrnambool 11
Cabrini 6
Bendigo 22
Darwin
Healthscope 5
Border MO
TOTAL RECRUITMENT
294
Recruiting ~6 per month
294 participants in total
Study target – 350
Total Recruitment

4. AIM 1 SUPER – Establishing a CUP cohort (1st April) 2019)
Item
Number
Target = 350
294 (84%)
56 remaining
Recruitment rate
6 per month on average
Projection: 30th Nov 2019
Item
Number
Female (%)
Age (SD)
Rural (%)
Deceased < 3 M (%)
< 6 M
< 9 M
< 12 M
Phase 1 [ ]
168
92 (55)
63 (13)
28 (17)
30 (18)
50 (30)
67 (40)
81 (48)
Phase 2 [2017 – ]
128
68 (53)
65 (13)
51 (40)
11* (10)
18* (23)
20* (32)
23* (46)
Combined
294
159 (54)
79 (27)
44* (15)
68* (28)
87* (38)
104* (48)
Test
Item
Number
Phase 2 data
128 samples
CCP
Complete
81 (63%)
Incomplete
41 (32%)
Pending
6 (5%)
SUPERDx
77 (60%)
44 (34%)
7 (6%)
Combined
Complete both
72 (56%)
Incomplete both
36 (28%)
Complete either
86 (67%)
* Number of included participants vary in P2 data as their duration on study will vary according to when they where recruited

5. AIM 2 SUPER – Impacting clinical decisions
Specific Aims:
Describe the molecular landscape of CUP patients and correlate molecular test results with demographic and clinical characteristics
Determine the impact site-of-origin and mutation profiling has had on treatment decisions taken by the treating clinician 13

6. Clinical impact of molecular testing Dr Tharani Sivakumaran
Design: Pre/post survey of clinical management prior to and post receiving genomic results Analysis ongoing

7. Early Results: Phase I Likely site of origin: CUPguide
CUPGuide was completed for ~78% (97 of 124) of samples
Primary site prediction was made in ~87% (84 of 97)
Predictions resulted in:
a change in management in ~12% (10 of 84)
confirmed current management in ~63% (53 of 84)
Mutation profiling: CCP version 1
Comprehensive Cancer Panel (CCP) was completed in ~83% (103 of 124)
Actionable gene mutations where identified in ~10% (10 of 103)
Germline gene mutations were identified in 6% (6 of 103)
a change in treatment for 30% (3 of 10) of patients because the targeted therapy was available.

8. AIM 3 SUPER – Quality of life and psychosocial needs
Specifically, we seek:
To establish reliable estimates for quality of life and psychosocial needs across the CUP illness trajectory
To identify similarities and differences between CUP and non-CUP patients from baseline to 12-month follow-up
To identify similarities and differences between urban and rural/regional CUP patients from baseline to 12-month follow-up

9. What do we know about the experience of CUP?
Compared to known primaries, CUP patients were:
less likely to receive written information about their type of cancer, diagnostic tests and any operations they had
Less likely to understand the results of their tests
Less likely to completely understand the explanation of their illness
Less likely to feel their views were taken into account in treatment discussions

10. Communicating with CUP patients
86 oncologist responded.
99% prepared to make a diagnosis of CUP if no primary located
BUT 27% prefer to provide a ‘best guess’ rather than CUP as an diagnostic entity
83% would assign a primary site to obtain PBS drug funding
62% did not have a specific treatment protocol for CUP
Different ways of describing Dx:
“No I don’t use CUP, I usually talk about my best guess primary” vs
“The primary (parent) appears of have regressed but metastases(children) have grown”

11. METHODS
Design
A prospective, longitudinal study with matched control group at baseline
CUP patients recruited from both urban and rural/regional
Patient reported outcome data will be collected at baseline and at 3, 6, 9 and 12 months post-baseline (or to death).

12. Measures
Physical, social and mental health Patient Reported Outcomes Measurement Interactive System (PROMIS®) : Anxiety; Depression; Fatigue; Pain Interference; Pain Intensity; Sleep Disturbance; Physical Function; Satisfaction with Social Roles and Activities
Cancer-specific health-related quality of life EORTC Quality of Life Questionnaire – C30 (EORTC QLQ-C30)
Medical communication/information and psychological needs: Needs Assessment for Advanced Lung Cancer Patients (NA-ALCP)
Hopelessness : Hopelessness Assessment in Illness (HAI)
Communication about and understanding of illness and treatment: a purpose-built questionnaire drawn from UK National Cancer Patient Experience Survey

13. Psychological distress in CUP patients: the role of communication
Aim To investigate the impact of patient-oncologist communication practices and socio-demographic factors on the anxiety and depression of CUP patients Design Cross-sectional survey: data drawn from baseline data from SUPER study.
Dr Kamil Wolyniec

14. Patients’ communication experiences
Item
Response scale
Percentage
How well do you feel you understand your cancer?
Very well
Well
Not so well
Not well at all
20%
43%
25%
12%
Were you given written information about the type of cancer you had?
Yes, and it was easy to understand
Yes, but it was difficult to understand
No, I was not given written information
I did not need written information
Don’t know/can’t remember
26% 9%
57% 7% 0%
How do you feel about the way you were told you had advanced cancer?
It was done sensitively
It should have been done a bit more sensitively
It should have been done a lot more sensitively
78%
16%

15. Results
CUP patients who felt they understood their cancer very well reported lower levels of anxiety and depression than those who did not.
Patient’s understanding of cancer
Patient’s understanding of cancer
p=.006
p=.029
p=.004
p=.040
p=.006
Mean Anxiety scores
Mean Depression scores
Very well
well
Very well
well
Not so well
Not well at all
Not so well
Not well at all

16. Key findings
Only 20% felt they understood their cancer very well and this was linked to lower levels of anxiety and depression
Less than half received written information about cancer or information about support but not linked to psychological distress.
Younger CUP patients reported higher anxiety and depression 28

17. Conclusions
Locating and retaining CUP patients in a cohort study remains challenging; as is successful genomic testing
Rapid advances in genomic testing to assist in the diagnosis and treatment but at present these advances don’t appear to be translating into clinical management change
Genomic testing advances represent a challenge for both clinician communication and patient understanding
Good patient understanding may alleviate psychological distress
Younger patients may require additional support and referral to psychological services