Cancer making a difference

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Cancer - making a difference in Greater Manchester
Dr Richard Byers
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Role of pathology in patient pathway
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http//www.cancer.gov/pdf/trwg/Barker-TRWG-RT-slid
es.pdf
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Targeted therapy Companion Diagnostics

• Targeted therapy implies a therapy with a
  specific molecular target
• DRUG MOLECULAR TARGET TARGETED THERAPY
• Predictive treatment modifiers, help match
  drugs to appropriate patient groups (eg HER2)
• Prognostic disease modifiers, correlate with
  disease outcome (PSA)

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Network Diagnostic Initiatives
Her 2 testing in breast cancer Cytology HPV
testing and LBC Greater Manchester and Cheshire
Haematological Malignancy Diagnostics
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HER FAMILY
Human epidermal growth factor receptor
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Node-negative breast cancer survival
HER2 status in breast carcinomas a prognostic
and predictive indicator
HER2

• HER2 ve breast carcinomas
• Have reduced
• Overall survival
• Disease free survival

Ross JS, Fletcher JA. Stem Cells 1998 16 413428
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Show resistance to traditional cancer
chemotherapies Have a better response to
aromatase inhibitors and anthracyclines may
respond to Trastuzumab (Herceptin)

• Women with HER ve early breast cancer given
  trastuzumab (Herceptin) in combination with
  adjuvant chemotherapy

• Treatment with Herceptin leads to approximately
• 50 reduction in the risk of recurrence
• 30 increase in overall survival

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UK HER2 testing algorithm
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0/1
Immunohistochemistry (IHC)
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Positive
Negative
Borderline
Reported as positive
Reportedas negative
FISH
Not amplified
Amplified
Reported as negative
Reported as positive
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Prof Mike Richards National Cancer Director
(Cancer Tsar)

• In 2005, NICE granted a licence for the use of
  Herceptin in the treatment of HER2 positive early
  invasive breast cancer
• October 2005 - the DH issued a directive that
  all early invasive breast carcinomas were to be
  tested for HER2 expression
• and that . there should be only one testing
  centre per Cancer Network .

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HER2 testing in Greater Manchester

• There are approximately 2800 3000 new breast
  cancers diagnosed each year in Greater Manchester
  and Cheshire
• The Greater Manchester Pathology Network decided
  to have 3 testing centres to cope with this
  significant number
• HER2 testing was already being carried out at the
  Bolton, Christie, Salford, Stockport and Wigan
  laboratories

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HER2 testing in Greater Manchester

• IHC testing at Christie, Salford and Stockport
• FISH testing at Christie
• Is centrally funded and
• Quality assured under the auspices of the
  HER2 PAG that was established in 2008 and is
  chaired by Anne Yates (BMS HoD, Salford).
• All patients with new invasive breast cancers
  in the Greater Manchester area now have full
  access to funded HER2 testing

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Morphology
Microarray chip analysis
Protein
Gene expression

• Acute leukaemia
• Lymphoma
• Breast cancer
• Others (prostate, brain, gastrointestinal,
  ovarian)

Indicator gene signatures
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Levels of diagnosis of haematological malignancy
PCR real-time PCR
Clinical features
Morphology
DIAGNOSIS
Flow cytometry
FISH
Microarrays
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NICE IOG for Haematological Cancers

• In order to reduce errors, every diagnosis of
  possible haematological malignancy should be
  reviewed by specialists in diagnosis of
  haematological malignancy. Results of tests
  should be integrated and interpreted by experts
  who work with local haemato-oncology
  multi-disciplinary teams (MDTs) and provide a
  specialised service at network level. This is
  most easily achieved by locating all specialist
  haemato-pathology diagnostic services in a single
  laboratory.
• Improving the consistency and accuracy of
  diagnosis is probably the single most important
  aspect of improving outcomes in haematological
  cancer.

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Central review diagnosis
Morphology (leukaemia) Flow cytometry PCR Ig /
TCR gene analysis
MRI / CMMC
Morphology (lymphoma) Flow cytometry Cytogenetics
FISH on LNs
Christie Hospital
Integration of tests into single report
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Greater Manchester and Cheshire Haematological
Malignancy Diagnostics (GMCHMD) service
Phase 1 Service

• Phase 1 concentrating on lymphoma diagnosis in
  paraffin embedded tissue live in December 07
• Dr Andrew Norton Lead Lymphoma
  Haematopathologist
• Approximately 1000 cases in first 10 months
  (matches estimated workload of 1200 pa)
• FISH testing established for lymphoma diagnosis
• PCR testing for immunoglobulin and T-cell
  receptor rearrangements established
• Integrated reporting of morphology,
  immunohistochemistry, FISH and PCR tests
• The mean turnaround time is 9 days from receipt
  of sample 6.3 days average for FISH and 16 days
  for PCR (expected to improve with new staff
  appointment). The overall average report time for
  an integrated report (including FISH and PCR
  where needed) is 15.4 days.

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Greater Manchester and Cheshire Haematological
Malignancy Diagnostics (GMCHMD) service
Benefits of the new service

• New diagnostic tests available in Network for
  lymphoma diagnosis
• Reduced turn around time for expert diagnosis
• Audit of first six months activity demosntrated
  an overall diagnostic revision rate of 37.9
• Of these 13.2 were critical / major and would
  have affected immediate clinical management, with
  a further 2 that would have possibly affected
  future management.

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IT is the key to service integration

• Implementation of protocols
• Co-ordination of results and reporting
• Communication with users
• Audit and quality assurance
• Workload measurement
• Linking to other clinical systems

• 250k for dedicated IT reporting and workflow
  management system for service granted by GMPNB
• Tendering in September / October 08
• Preferred bidder being identified
• Planning for implementation by end March 09

250k from Pathology Network Board to develop
implement IT system OBS being finalised for
tender late 07 and delivery spring 08
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Future Technologies
New Flow methods and cell sorting Mutational
analysis Bioinformatics Global assessment of
gene expression Constitutional genetic analysis
Conventional cytogenetics Bone marrows Single
colour Immunocytochemistry Morphology
The future may not be more expensive but there
are transitional costs
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North West Cytology Workforce Drivers for Changes

• Decreasing Volumes
• Quality
• Ageing workforce
• New Technologies
• HPV testing and vaccination
• Semi-automation
• Latest guidance on volumes and turnaround times

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Total laboratory workloads 2002, 2006, 2007
2008
From Dr. Turnbull, QA Director/ NW Cervical
screening programme
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QualityRecent ScHARR Report

• Minimum recommended workload 35000
• South sectors workload 2009-10
• MCC 70000
• Stepping Hill 24000
• Tameside 10500
• Combined SHTH 34500

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Semi automation

• 2 machines in MAVARIC Trial
• Manchester is running HTA funded trial 100,000
  samples since 2006 for both machines
• Trial due to finish and report in 2009
• The results so far are very favourable for very
  fast and reliable screening
• If accepted nationally then further 20 reduction
  of Sure path LBC work as computer decides the
  negative result

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Modern Manchester Cytology LabTesting site for
semiautomation
Hologic Imager
BD Focalpoint GS suitable for SH and
MCC suitable for TH and MCC
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Hologic system Suitable for SH and MCC
Increased productivity
Screening of only 22 areas Currently screening
75000 cells
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BD FocalPoint GS Imaging System
suitable for TH and MCC
20 smears no need to screen Screening of only
10 areas in remaining smears Increased
Productivity and Reduced Workload
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HPV Testing and Vaccination

• Limited HPV testing will start nationally from
  2009
• Reduction in workload by at least 10
• Manchester was funded by HTA to run the trial of
  35000 women to see the effect of HPV test with
  cytology for all women-ARTISTIC Trial
• The trial just completed and the results are
  showing that limited testing is very good but it
  is not cost effective to test all women at the
  moment
• Post vaccination women from 2015 will require HPV
  test to see the protection from vaccine therefore
  from 2015 HPV test is likely to replace cytology

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Cervical Screening Post VaccinationFrom 2015
(Crystal Ball Gazing)

• Age 25 first test in all women by HPV only. No
  cytology
• Currently 70 are HR HPV-ve at 25 years. No
  further test for 10 years. No cytology
• Around 10 are 16/18ve and could be negative
  post vaccination. No cytology.
• So, perhaps only 20 could be considered at
  risk by testing HR HPVve requiring a further
  test by cytology.
• 80 reduction in cytology workload

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GIST
CD117
KIT
Imatinib