Module - Solid Tumours 2 (SLS430)

STP

Aim of this module

 This module provides trainees with a detailed understanding of the molecular mechanisms of lung and ovarian cancer and the associated genomic testing. With these exemplars trainees will develop an understanding of the organisation and delivery of a complex cancer genotyping service. They will perform common laboratory methods, interpret genomic results and develop an understanding of the need for additional investigations as well as use of associated targeted therapies. Trainees will build upon previous knowledge gained in the context of relapse, metastasis, resistance, as well as the roles of first and second line therapeutics. Furthermore, this module will increase the knowledge base for applications to monitor disease and use less-invasive sampling strategies. They will consider how this impacts on patient management, personalised medicine and therapeutic options. They will also develop an awareness of common central nervous system (CNS) tumours. Trainees will understand the contribution of germline mutations to cancer and the implications for patients and their families. They will recognize the importance of cross-discipline cancer genomic analysis.

Work-based learning outcomes


Using lung and ovarian cancer;

  1. Interact with relevant disciplines and apply appropriate approaches for the diagnosis and treatment of example conditions
  2. Recognise the main clinical features and morphological characteristics of lung and ovarian cancer.
  3. Compare the routes of referral of patients for genomic testing from a range of clinical settings.
  4. Apply the appropriate genomic testing strategy set in the context of the patient treatment pathway.
  5. Appreciate the role of ctDNA in diagnosis and monitoring of disease
  6. Interpret and report on the relevant laboratory procedures for the diagnosis and monitoring of the patient.
  7. Understand the assignment of risks and likelihoods based on the results of tumour analysis and the response to chemotherapy.
  8. Describe the implications of the identification of somatic and germline variation in tumour samples for the patient and their family.

Work-based Competencies


Learning outcome Title Knowledge
1 1,2,3,4

Select the correct genomic tests for a range of lung and ovarian cancer referrals and sample types

  • The principal referral reasons that would indicate testing for the conditions under investigation.
  • The clinical and scientific basis for the repertoire of genetic testing available to investigate the common range of clinical referrals.
  • Ethical issues associated with patient consent.
  • The clinical utility of genetic testing in patients with cancer. The overlapping and complex testing pipelines where patients referred with cancer.
  • This analysis in the context of any previous pathology testing for the patient.
  • National guidelines for the laboratory investigation of cancer including standard of care testing.
  • Appropriate choice of assays according to clinical details and other laboratory findings.
  • The importance of sample quality
  • Consideration of germline mutation and the potential for incidental findings
2 2,4

Perform morphological identification of tumour material for lung and/or ovarian cancer.

  • The use of a range of staining techniques
  • Cancer classification: Staging; Morphology; Pathology; Therapeutic; Gene expression.
  • The importance of assessing cellularity and percentage tumour nuclei/tumour burden
  • Recognising necrosis
  • Factors affecting successful completion of procedures through pre-analytical factor such as ischaemia time; fixation; processing; tumour block selection; paraffin block storage; cross contamination.
  • Identification of samples and documentation
3 4,5,6

Perform and interpret genomic testing to identify single nucleotide variation for patients referred with lung cancer

  • The technical pathway including its limitations and sensitivities and the essential requirement for good laboratory practice and the risks.
  • Standard of care testing and the value of targeted analysis
  • How to identify and describe the potential for error, how this is mitigated and its potential effects.
  • Best practice guidelines compared with laboratory practice and any differences between the two.
  • Clinical and scientific aspects of lung cancer.
  • The use of digital, light and fluorescent microscopy.
  • The use of HGVS.
  • Internal and external quality assurance (QA) for genomic analysis.
  • Local laboratory procedures for recording results of genomic analysis.
  • How to critically appraise relevant literature and databases.
4 4,6

Perform molecular investigations for identifying fusion gene translocations which may impact patient management.

  • Health and safety requirements for processing cancer samples.
  • Scientific principles of immunohistochemistry and FISH.
  • Molecular and cellular changes in cancer detected by immunohistochemistry and FISH.
  • Preparation of slides for immunohistochemistry and FISH.
  • Use of microscopes.
  • Limitations of each procedure including limit of detection, sensitivity and specificity.
  • Factors affecting the quality of samples for immunohistochemistry and FISH.
  • The use of sequence based strategies for the detection of gene fusions
  • Interpretation of results.
  • Integration of results with other laboratory test results.
  • Therapeutics available and impact of results Internal quality controls for assays.
  • Importance of external quality assurance schemes.
  • Role of validation and verification of procedures and equipment.
  • Laboratory accreditation schemes – ISO 15189 or equivalent.
  • National guidelines for care pathways and procedures.
5 6

Use appropriate bioinformatics analysis of genotyping results.

  • Awareness of different bioinformatics pipelines available and their limitations
  • Identifying sequence variants of unknown significance and how to categorise them following best practice guidelines
  • The importance of internal quality control and other quality parameters.
  • Targeted versus screening approaches(gene panels vs whole genome analysis)
  • The use of appropriate databases and tools
  • The principals of data storage, sharing and management.
6 5,6

Perform analyses and interpret genomic results from non-invasive liquid biopsy samples

  • Sample suitability
  • Extraction methodologies for circulating free tumour DNA from liquid biopsies
  • Principles of the technique, including limitations and sensitivity. Internal and external quality control.
  • The quality parameters for the test.
  • Use of suitable analysis software and bioinformatics tools. How to recognise samples that require repeat testing or that have failed testing.
  • Accurate recording of results of analysis following local laboratory protocols.
7 6,7,8

Prepare a range of diagnostic clinical reports for a lung cancer patient.

  • How to recognise all tests have been completed to a satisfactory standard for the referral reason.
  • All information has been validated as correct. Selection of correct report template for referral reason.
  • Recommendations for further referral (e.g. clinical genetics). Identify the requirements for any follow up testing, the testing methods available and the appropriate choice of test. Describe any limitations.
  • Use of correct scientific terminology and nomenclature (e.g. HGVS).
  • Communication of complex scientific information to clinicians and patients.
  • Recommendation of suitable potential therapeutics including personalized medicine e.g. Monoclonal Antibody therapy, Tyrosine kinase inhibitor therapy (primary and secondary), Clinical trials, NICE and Cancer Drug Fund
  • The importance of sensitising and resistant mutation
  • Best practice guidelines compared with laboratory practice and any differences between the two.
  • How to identify pertinent EQA schemes; their role and practice; how these are incorporated into laboratory practice; ISO standards for lab participation in EQA schemes.
  • The calculation of residual probability following molecular testing where appropriate.
  • Use of relevant databases and the literature in the interpretation of results.
  • Pathways for obtaining further suitable samples
8 6,7,8

Produce a diagnostic report for an ovarian cancer patient which should include germline mutation and appropriate additional information.

  • Interpretation of results including diagnostic and treatment recommendations, taking into account the relationships between genetic markers, other testing modalities and clinical diagnosis. Use and critical appraisal of relevant literature and online databases.
  • Role of multidisciplinary team (MDT) meetings and guidelines such as Improving Outcomes Guidance and NICE Guidelines. Recognising all tests have been completed to a satisfactory standard for the referral reason.
  • All information has been validated as correct. Selection of correct report template for referral reason.
  • Recommendations for further referral (e.g. clinical genetics). Identify the requirements for any follow up testing, the testing methods available and the appropriate choice of test. Describe any limitations.
  • Use of correct scientific and clinical terminology.
  • Use of relevant databases and the literature in the interpretation of results.
  • Communication of complex scientific information to clinicians and patients.
  • Best practice guidelines compared with laboratory practice and any differences between the two.
  • How to identify pertinent EQA schemes; their role and practice; how these are incorporated into laboratory practice; ISO standards for lab participation in EQA schemes.
9 1,3,6,

Observe a clinic where a patient is being given results of laboratory tests that include genetic analysis. Reflect on this experience and present to colleagues

  • Information regarding potential outcomes of a genetic test
  • Implications of the genetic results for diagnosis/prognosis
  • The role of the Healthcare professional providing the information to the patient
  • Principals of patient centred care
  • Interaction with patient
  • Consent issues (for patient testing and for observation by a trainee)
  • Professional behaviour
  • Role and process of active listening
10 1,3,6,8

Assist with the preparation of cases to be discussed and reviewed in an MDT meeting with other healthcare professionals

  • Integration of laboratory and clinical findings for a final diagnosis
  • Identification of the most appropriate treatment Monitoring of residual disease
  • Role of NICE and clinical trials
  • National and international studies and projects

Work-based assessment


Complete 3 Case-Based Discussion(s)
Complete 3 of the following DOPS and/or OCEs
Type Title
DOPS Perform morphological assessment on lung and ovarian tissue, demonstrating awareness of cellularity, necrosis and tumour material.
DOPS Perform DNA extraction of suitable samples types other than FFPE material, such as fresh tumour and liquid biopsies.
DOPS Describe and perform technologies suitable for tumour genotyping and identifying fusion gene translocations.
DOPS Perform tumour genotyping analysis using bioinformatics pipelines and associated tools.
DOPS Produce a diagnostic clinical report for a patient with familial ovarian cancer.
DOPS Prepare a draft report for an inappropriate referral received.
OCE Participate in an MDT meeting with other healthcare professionals
OCE Discuss patient results with a healthcare professional telephone or in person
OCE Discuss implications of receiving an unlabeled sample with a healthcare professional.
OCE Discuss an inappropriate referral with a healthcare professional

Module authors and contributors


Authors: Victoria Hewitt

Contributors: Jennie Bell, Anthony Bench, Michelle Bishop, Rachel Butler, Rosalind Ganderton, Victoria Hewitt, Emma Jenkinson, Sheila O’Connor, Anneke Selle