Diagnosing Pancreatic Cancer - Challenges and Developments - PCUK 15TH October 2018

 
Diagnosing Pancreatic Cancer - Challenges and Developments - PCUK 15TH October 2018
Diagnosing Pancreatic
    Cancer – Challenges
      and Developments
               PCUK 15TH October 2018

                       Dr Andrew Millar
MDC Clinical Lead UCLH Cancer Alliance

     Gastroenterologist and Hepatologist
     North Middlesex University Hospital
                    Royal Free Hospital
Diagnosing Pancreatic Cancer - Challenges and Developments - PCUK 15TH October 2018
The Problem of Cancer Diagnosis and
         Survival in the UK

                                      2
Diagnosing Pancreatic Cancer - Challenges and Developments - PCUK 15TH October 2018
BENCHMARKING DATA HIGHLIGHTS A SURVIVAL GAP
 Although an improving picture, cancer survival in the UK trails behind comparable countries

                                                                             Source: International Cancer
                                                                             Benchmarking Partnership M1 - 5
                                                                             year survival, 1995-2007.
                                                                             Published 2011

 Providing increased impetus amongst professionals in the UK to improve early diagnosis
Slide courtesy of Sara Hiom – CRUK
Diagnosing Pancreatic Cancer - Challenges and Developments - PCUK 15TH October 2018
UK HEALTH SYSTEM IS NOT SET UP FOR EARLY DIAGNOSIS
  The UK, versus other comparable countries, has:
  • Focus on Alarm Symptoms
  • Less investigation of low risk symptoms
  • Less access to diagnostics and specialists

                                                    Source: International Cancer Benchmarking
                                                    Partnership M3 - Survey 2012-2013. Published 2015

Amended slide courtesy of Sara Hiom – CRUK
Diagnosing Pancreatic Cancer - Challenges and Developments - PCUK 15TH October 2018
Background
Current cancer pathways are unsustainable and not fit for purpose

                                                                                                          Key findings of 2ww
                                                                                                          referrals
                                                                                                        NICE guidance (NG12)
                                                                                                         2ww pathways - 3% cancer
                                                                                                         conversion

                                                                                                        Most cancers (>50%) are
                                                                                                         not diagnosed on 2ww
                                                                                                         pathway

                                                                                                        A quarter (25%) diagnosed
                                                                                                         on routine pathways
        In the last 3 years 2ww referrals
        have risen by 17%                                                                               A fifth (21%) are diagnosed
                                                                                                         via A&E

Source: Collated by Centre for Cancer Outcomes. In strictest confidence for NHS internal use only. CRUK website:                   5
http://www.cancerresearchuk.org/health-professional/cancer-statistics/diagnosis-and-treatment#heading-Zero
Diagnosing Pancreatic Cancer - Challenges and Developments - PCUK 15TH October 2018
Early Diagnosis of Pancreatic Cancer
 The problem (opportunity) of symptoms

                                         6
Diagnosing Pancreatic Cancer - Challenges and Developments - PCUK 15TH October 2018
Hard for Patients
Symptom appreciation - Hard to be ‘Clear on Cancer’
when the symptoms are so common (and GP access?)

 “Greater public and healthcare professional awareness of the combinations of
 subtle and intermittent symptoms, and their evolving nature, is needed to
 prompt timelier help-seeking and investigation among people with symptoms
 of pancreatic cancer” Mills K et al. BMJ Open 2017;7                           7
Diagnosing Pancreatic Cancer - Challenges and Developments - PCUK 15TH October 2018
Hard for Doctors
                The NG12 Symptom Based Infogram1

Assessing and referring adult cancers. Image from Suspect cancer (part 2- adults) BMJ 2015;350:h3044
Diagnosing Pancreatic Cancer - Challenges and Developments - PCUK 15TH October 2018
Why is PDAC so difficult to diagnose in primary care?

• >30,000,000 consultations for abdominal symptoms per
  year in the UK

• Early symptoms non-specific

• 0.02% are pancreatic cancer

• GP access to CT scanning

• No adequate diagnostic biomarkers

• NG12 / 2WW guidance is better for specific symptoms
Diagnosing Pancreatic Cancer - Challenges and Developments - PCUK 15TH October 2018
The Problem of Symptoms in Pancreatic Cancer
• Non-specific symptoms – abdominal pain, weight loss,
  backache, fatigue, (NSCS) & new NIDDM
• Symptom Study – 93% of patients had relevant symptoms
  up to 2 years before diagnosis1
• Delay is similar to other cancers with non-specific
  symptoms also diagnosed late2
• Patients often seen multiple times by GP – Av 3.23
• Consequence - Symptomatic PDAC usually stage 3-4
• How can we improve this?

1Keane MG, et al. BMJ Open 2014
2Dengsø  KE et al J Neoplasm. 2017; 5: 2
3Lacey K et al Med J Aust 2016; 205 (2): 66-71            10
Diagnosis of Pancreatic Cancer
• Symptomatic – 95%
  – Symptom Appraisal – patient understanding
  – Help-seeking – patient attitude, accessibility
  – Diagnostic – HCW attitude, availability of
    tests, referral pathways, waiting times
• Asymptomatic – 5%
  – Screening – identification of high risk people
  – Surveillance – of identified lesions e.g. IPMN

                                                     11
Symptomatic Cancer
Anderson Model of Patient Delay
   Walter et al J Health Serv Res Policy Vol 17 No 2 April 2012

                                                                  12
Benefits of Early Diagnosis
      • Increase survival by increasing resection rates
            – currently 20% operable, 5% 5-year survival
      • If we could detect earlier survival would improve
            – ~30mm - survival 10-20%
            –
Key Points on Diagnosis
• CT scan before ERCP – latter with brushings
• If no diagnosis FDG-PET / EUS – latter with cytology
• CT or MRI for cysts - refer if jaundice/solid/dilated PD
• EUS for cysts with aspiration for Cytology and CEA

                                                             14
Key points on Surveillance
• Surveillance for pancreatic cancer to people with:
   – Hereditary pancreatitis and a PRSS1 mutation
   – BRCA1, BRCA2, PALB2 or CDKN2A (p16) mutations and one or
     more first-degree relatives with pancreatic cancer
   – Peutz–Jeghers syndrome
   – 2 or more first-degree relatives, across 2 or more generations
   – Lynch syndrome (mismatch repair gene [MLH1, MSH2, MSH6 or
     PMS2] mutations) and any first-degree relatives
• Surveillance by MRI / EUS / CT
                                                                      15
Current imaging diagnostic tests

 • CT scan – misses 23% of small cancers1
 • MRI – identifies 80% those not seen at CT2
 • FDG-PET – best sensitivity (89%)
 • EUS sensitive and allows needle aspiration but
   limited availability
 • None of these yet widely available in primary
   care – increasing however

1Wong    J.C et al Clin. Gastroenterol. Hepatol. 2008;6:1301–1308
2Kim   J.H et al Radiology. 2010;257:87–96
                                                                    16
Biomarkers – active research area

                                                                  17
Reproduced from Zhang X et al Am J Cancer Res 2018;8(3):332-353
Multi-Disciplinary Diagnostic Centres

                                        18
Symptomatic Cancer
Anderson Model of Patient Delay
   Walter et al J Health Serv Res Policy Vol 17 No 2 April 2012

                                                                  19
What are MDCs?
MDC pathway: avoiding the hospital pinball machine

                                                     20
21
What are MDCs?
MDC pathway

                 1. Fast track diagnostic centre/clinic for suspected cancer
    What is an
                    where existing 2WW pathway is unclear or not suitable
     MDC?
                 2. MDC runs within a hospital and uses current hospital infrastructure

                 1.   CT
                 2.   Bloods
       Main      3.   Endoscopy
    Diagnostic   4.   Colonoscopy
       tests     5.   MRI
                 6.   PET CT
                 7.   ERCP

                 1. Named CNS contact from time referral is received
     Benefits
                 2. Fast access to diagnostics
                 1. If shown to be beneficial will be rolled out nationally
     Future
                 2. Opportunity to support more DIRECT and STRAIGHT TO TEST

                                                                                          22
MDCs align with national and local strategy
Danish Model – more GP access to tests

                                                                                               Aligns with     Aligns
       Potential                   Area of benefit   Rationale                                   national    with NCL
                                                                                                strategy?    strategy?
    benefits of MDCs
                                   Diagnosis within •Rapid access to diagnostics
                                   28 days          •Improves patient experience                              

      Improve
     quality and
                                   Aid treatment
                                   within 62 days
                                                     •Earlier diagnosis in pathway Will
                                                      improve survival rates                                  
     outcomes
                                                     •Cancer diagnosis following ED poorer
                                   Reduction in
                                   A&E cancer
                                                      outcome, even when controlling for                      
                                                      other factors1
                                   diagnosis
                                                     •Better use of hospital resources
      Improve
       patient
     experience
                                   Diagnosis
                                   through
                                                     •Patients benefit from CNS support                       
                                   appropriate       •Better access to diagnostic tests and
                                   setting            specialist cancer and holistic support

    Reduction in                   Reduction in      •Reduce number of GP visits
       cost                        number of
                                   wasted            •Reduce incorrect referrals Meets
                                                      needs of primary care
                                                                                                              
                                   consultations
                                                                                                                  23
1 - Plaser TR et al 2013; Schneider C et al. 2013
THERE ARE 10 MDCS ACROSS ENGLAND                                    • A common dataset
                                                                       agreed across the
                                                                       projects
Airedale, Wharfdale &                   Leeds
Craven                                  MDC site: St James           • Comparator data for
MDC site: Airedale                      University Hospital
General Hospital                        (Specialist Cancer Centre)     each project area; only
                                                                       partial data and largely
                                                                       retrospective audits
Greater Manchester
MDC sites: Manchester
University NHS
                                                                     • National Cancer
Foundation Trust                                                       Diagnosis Audit used to
(Wythenshawe
Hospital) and The                                                      create a ‘proxy
Northern Care Alliance
(Royal Oldham
                                        London                         comparator pathway’ for
                                        MDC sites: North
Hospital)                               Middlesex University           NSCS patient cohort
                                        Hospital, University
                                        College London Hospital      • Collection of MDC data is
                                        (Specialist Cancer
                                        Centre), Southend              ongoing (expect final
Oxford
MDC site: Oxford
                                        University Hospital,           cut-off for evaluation to
                                        Queens (BHRUT) and the
University Hospital
Trust (Specialist Cancer
                                        Royal Free Hospital            be end July 2018)
Centre)

   A national approach allows different NHS settings to be explored and creates a larger MDC
                                  referral data set for analysis
Project overview
North London MDC referral criteria and MDC sites

  Who to refer

   Current main indications
   1. New unexplained
      abdominal pain
                                                     North Middlesex
   2. Unexplained weight loss
                                        Royal Free
   3. Painless jaundice                                  Barts Health   BHRUT
   4. New and persistent
      unexplained nausea / loss
      of appetite
                                            UCLH
   5. GP has concern /gut feeling
      of an underlying
      gastrointestinal (GI) cancer
                                                                           25
Project overview
Case study
 Patient referred in June 2017

                        1                Referral received
                                                                                Day 0-1
                        2            Referral triaged by CNS

                        3              Patient seen in MDC                       Day 3

                                           CT

                                                                  Diagnostics
                        4    ERCP / bile duct brushing
                                                                                Day 3-5

                                     Upper GI MDT

                        4         Patient informed of diagnosis                  Day 9

                                                                                             Diagnosed
                                                                                           within 28 days:
                        5        Imaging sent to RLH for discussion
                                                                                            treated in 41
                                                                                                days
                        6 Patient seen by surgeon and informed of               Day 9-41
                                            care plan

                        7                    Surgery

                                                                                                             26
MDC Performance Data

                       27
NATIONAL FIGURES - CANCER DIAGNOSES BY MDC UNTIL END FEB
2018
MDC                    Number of  Number of   Conversion
                           cases    cancers      rate
           Airedale         187       18          10
Greater    Royal Oldham     119       17          14
Manchester
           Wythenshawe      187       13          7
           Leeds            326       27          8
London     Queen (BHRUT)    119       8           7
           North            103       6           6
           Middlesex
           Royal Free        8         -          -
           UCLH             281       10          4
           Oxford           293       43          15
Total                      1,623     142          9
MDC outcomes
National figures - Diagnosis of MDC patients
    Cancer Diagnosis                   Non-cancer Diagnosis
               30                      Broad Description                                                    N     %
                                       Diseases of the digestive system                                     166   39
                                       Symptoms, signs and abnormal clinical and laboratory findings,
               25                                                                                           44    10
                                       not elsewhere classified
                                       Diseases of the respiratory system                                   42    10
                                       Diseases of the genitourinary system                                 31     7
  Percentage

               20
                                       Neoplasms (benign)                                                   28     7
                                       Diseases of the musculoskeletal system and connective tissue         20     5
               15                      Diseases of the circulatory system                                   19     5
                                       Certain infectious and parasitic diseases                            14     3
                                       Endocrine, nutritional and metabolic diseases                        14     3
               10
                                       Mental, Behavioural and Neurodevelopmental disorders                 14     3
                                       Diseases of the blood and blood-forming organs and certain
                                                                                                            13     3
                                       disorders involving the immune mechanism
               5
                                       Congenital malformations, deformations and chromosomal
                                                                                                             6     1
                                       abnormalities
               0
                                       Diseases of the nervous system                                        4     1
                                       Diseases of the skin and subcutaneous tissue                          2     0
                                       Injury, poisoning and certain other consequences of external
                                                                                                             2     0
                                       causes
                                       Factors influencing health status and contact with health services    2     0
                                       Grand Total                                                          421   100

                                                                                                             29
North London MDCs April 18- Oct 18
                                                                                                  Referral numbers and reason
 Number of patients referred between April 17 – Sept 18                                                                                                                                        Referral reason
                                                                                                                                                                                               400

                                                                                                                                                                                               350
                  60
                                                                                                                                                                                               300
                  50
                                                                                                                                                                                               250
                  40
                                                                                                                                                                                               200
                  30
                                                                                                                                                                                               150
     No of patients

                  20
                                                                                                                                                                                               100
                  10
                                                                                                                                                                                               50
                      0
                                                                                                                                                                                                0
                                                                                                    Dec-17
                            Apr-17
                                     May-17

                                                                                                                                Mar-18
                                                                                                                                         Apr-18
                                                                                                                                                  May-18
                                              Jun-17
                                                       Jul-17

                                                                                  Oct-17
                                                                Aug-17

                                                                                                                                                           Jun-18
                                                                                           Nov-17

                                                                                                             Jan-18

                                                                                                                                                                             Aug-18
                                                                         Sep-17

                                                                                                                      Feb-18

                                                                                                                                                                    Jul-18

                                                                                                                                                                                      Sep-18
                              Ma                                                                                               Ma     Ma
                          Apr    Jun Jul- Aug Sep Oct Nov Dec Jan- Feb                                                            Apr    Jun Jul- Aug Sep
                              y-                                                                                               r-     y-
                          -17    -17 17 -17 -17 -17 -17 -17 18 -18                                                                -18    -18 18 -18 -18
                              17                                                                                               18     18
UCLH                      14 12 22 19 24 25 24 35 31 36 39                                                                     26 42 45 51 40 43 37
                                                                                                                                                                                                             UCLH   NMUH   BHRUT   RFH
BHRUT                      0         1        3        2 13 11 10 17 11 13 14 13 14 13 27 52 42 0
NorthMid                   0         1        1        8        4        9 12 13 16 19 20 24 9                                                    9 21 27 20 10
Royal Free 0                         0        0        0        0        0        0        0        0        0        9 12 20 19 21 37 23 28                                                              Referral numbers in August-
                                                                                                                                                                                                           September are lower
                                                                                                                                                                                                          E-referral’s has gone live

Source: UCLH, North Middlesex , Royal Free and BHRUT data
North London MDCs April 18- Oct 18
                                              Diagnosis and cancer conversion rate
               350
               300
               250
               200
               150
               100
                50
                 0
                                      Cancers                            Non cancer                       All Test normal
           North Mid                     7                                   77                                  98
           BHRUT                         10                                  40                                  60
           UCLH                          28                                 287                                  96
           Royal Free                    5                                   48                                  49

                                                   North Mid     BHRUT     UCLH       Royal Free

   Cancer conversion rate

    Site
                  Number of    Cancer conversion    Time to cancer     Cancer conversion rate at ULCH is currently on 4.95 % this
                   referrals          rate         diagnosis (mean)     may increase still awaiting outcomes for 2 more patients .
   UCLH              565            4.95%               36.8           Time to cancer diagnosis very good with North Middlesex
 North Mid           223            2.81%               25.5            currently averaging on 25.5 days.
  BHRUT              256            3.90%               36.1           All sites need to improve in data entry of outcome status and
 Royal Free          169            2.88%               42.6            date communication.

Source: UCLH, North Middlesex , Royal Free and BHRUT data
North London MDCs April 18- Oct 18
                                                    Types of Cancer
        9
        8
        7
        6
        5
        4
        3                                                                       TOTAL
        2                                                                       ULCH
        1
        0                                                                       BHRUT
                                                                                NORTH MID
                                                                                ROYAL FREE

        Highest number are Pancreatic, Colon and Lung cancer with total of 8 (16%) each

Source: UCLH, North Middlesex , Royal Free and BHRUT data
1   2   3   4

                                           North London MDCs
                                            Patient Experience

     Patient experience
                                                             80% of patients are
90
                                                              extremely likely to
                                                              recommend the MDC
80                                                            service to family and
70                                                            friends
60                                                           82.8 % felt they received
50                                                            their first hospital
                                                              appointment as soon as
40
                                                              was necessary
30
                                                             89.3% felt their test results
20                                                            were explained in a way
10                                                            they could understand
 0                                                           78.6% felt they waited a
      Extremely    Likely   Neither     Don’t   Not likely    reasonable amount of time
        likely              likely or   know
                            unlikely                          while attending clinics and
                                                              appointments
MDC Challenges and Opportunities
            Challenges                       Opportunities
•   Creating the team –            •   Model of care clarified –
    clinicians and CNS                 and to be enhanced
•   Trust support - Clinic space   •   Strong CCG/GP support
    and consultant time            •   2WW pathway on ERS
•   GP education                   •   Pathway for rejected
•   Integrating into CCG and           referrals developing
    Trust referral systems         •   Develop A&E pathway
•   Excessive inappropriate        •   Is potential model for FDS
    referrals – conversion rate    •   London Research Network
•   Currently speeds diagnosis         developing
    but not improving stage

                                                                    34
So what do we need?
•   Better awareness of the ‘pattern’ of cancer symptoms
•   Manage population risk – obesity, smoking, alcohol (pancreatitis)
•   Faster diagnostic pathways (MDCs)
•   Identify high risk population and screening/surveillance methods
         –   Hereditary pancreatic cancer (5-10% of PC)
         –   IPMN surveillance – all need monitoring
         –   New diagnosis of Diabetes – 1% > 50 yrs in 3 years1
         –   Acute pancreatitis – 1.5-6.3% in 2 years 2, 3
         –   Chronic pancreatitis 1 and 4% risk of PD over 1 and 20 yrs4
         –   Other genetic syndromes – Lynch, Peutz-Jeghers
• Better biomarkers

1ChariS.T. et al Gastroenterology. 2005;129:504–511
2Kimura Y. et al. Intern. Med. 2015;54:2109–2114
3Munigala S. et al. Clin. Gastroenterol. Hepatol. 2014;12:1143–1150.
4Lowenfels A.B.et al International Pancreatitis Study Group. N. Engl. J. Med. 1993;328:1433–1437.
                                                                                                    35
The Future for Early Diagnosis of Pancreatic Cancer

•   Patient awareness
•   GP training and direct access to tests
•   Blood / Urine biomarkers
•   Rapid diagnostic pathways - MDCs
•   Increase screening and surveillance

                        Thank you
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