Solid Cancers 1 —
Training activity: 5

Details

Analyse and interpret DNA and RNA NGS data for sequence variants (SNV, SV), copy number variants (CNV) and fusion genes where applicable for:

• Colorectal
• Lung
• Melanoma

Type

Entrustable training activity (ETA)

Evidence requirements

Evidence the activity has been undertaken by the trainee repeatedly, consistently, and effectively over time, in a range of situations. This may include occasions where the trainee has not successfully achieved the outcome of the activity themselves. For example, because it was not appropriate to undertake the task in the circumstances or the trainees recognised their own limitations and sought help or advice to ensure the activity reached an appropriate conclusion. ​

Reflection at multiple timepoints on the trainee learning journey for this activity.

Reflective practice guidance

The guidance below is provided to support reflection at different time points, providing you with questions to aid you to reflect for this training activity. They are provided for guidance and should not be considered as a mandatory checklist. Trainees should not be expected to provide answers to each of the guidance questions listed.

Before action

What does success look like?

• Identify what is expected of you in relation to effectively analysing and interpreting NGS data for solid tumours, specifically colorectal and lung cancer, and melanoma. This involves analysing, interpreting, and evaluating the clinical significance of variants using a range of bioinformatics tools and best practice guidelines.
• Discuss with your training officer to gain clarity of what is expected of you in relation to applying current nomenclature (e.g., for genomic alterations) and verifying the clinical relevance of findings before they proceed to reporting.

What is your prior experience of this activity?

• Think about what you already know about analysing and interpreting genomic data or utilising bioinformatics tools. Have you previously interpreted low-level variants or complex genomic aberrations?
• Consider possible challenges you might face during the activity, such as distinguishing complex genomic aberrations from artifacts, troubleshooting bioinformatic pipeline flags, or integrating conflicting evidence regarding the clinical significance of a variant, and think about how you might handle them.
• Recognise the scope of your own practice for this activity i.e. know when you will need to seek advice or help, and from whom. You will need to seek advice from your Training Officer when required, for example if encountering a variant of uncertain significance or if the interpretation contradicts established guidelines for colorectal and lung cancer, or melanoma.
• Acknowledge how you feel about undertaking the critical responsibility of interpreting complex NGS data that directly informs patient management for solid cancers.

What do you anticipate you will learn from the experience?

• Consider the specific skills you want to develop, such as mastering the use of specific genomic databases or refining your systematic approach to evaluating variant pathogenicity.
• Identify the specific insights you hope to gain into understanding the prognostic and predictive value of specific genomic aberrations (e.g., driver and passenger mutations) in colorectal and lung cancer, and melanoma.

What additional considerations do you need to make?

• Consult actions identified following previous experiences of data analysis or variant interpretation.
• Identify important information you need to consider before embarking on the activity, such as reviewing the specific academic content on molecular mechanisms leading to solid cancers, current nomenclature for genomic alterations, and the analytical sensitivity/limits of detection (LOD) of the NGS assay used to ensure reliable interpretation of low-level variants.

In action

Is anything unexpected occurring?

• Are you noticing anything surprising or different from what you anticipate whilst processing and making sense of complex NGS data?
• Are you encountering situations such as:
  • Unexpected or rare variants (e.g., complex genomic alterations) that require careful interpretation beyond routine findings?
  • Difficulties with the bioinformatic pipeline or analysis tools?
  • Data quality issues impacting analysis?
  • The results show a finding that conflicts with the known aetiology of colorectal and lung cancer or melanoma?

How are you reacting to the unexpected development?

• How is this impacting your actions? For example, are you responding to the situation appropriately? Are you consulting databases, colleagues, or guidelines immediately? Are you adapting or changing your approach to data analysis by manually checking alignment or re-running specific analysis tools?
• Consider the steps you are taking in the moment, such as immediately cross-referencing a rare variant in multiple genomic databases or consulting the specific academic content on complex genomic alterations.
• How are you feeling in that moment? For instance, are you finding it difficult to adapt your initial analysis workflow? Is it affecting your confidence in ensuring the data interpretation is robust?

What is the conclusion or outcome?

• Identify how you are working within your scope of practice. For example, are you successfully correlating the complex genomic alterations with known prognostic data? Or are you needing support because the variant classification suggests central involvement or a highly novel finding requiring expert input?
• What are you learning as a result of the unexpected development? For example, are you mastering a systematic technique for evaluating data quality issues when they impact variant calling?

On action

What happened?

• Begin by summarising the key steps you took when analysing and interpreting the NGS data for the colorectal, lung and/or melanoma cases.
• Consider specific events, actions, or interactions which felt important, such as how you utilised bioinformatic tools/pipelines to identify specific variants or genomic alterations or how you integrated different types of data (e.g., sequence alignment, variant calls) to reach an interpretation.
• Include any ‘reflect-in-action’ moments where you had to adapt to the situation as it unfolded, for instance, immediately re-running a variant call filter when the initial pipeline suggested a novel, highly complex rearrangement that challenged known genomic mechanisms in colorectal cancer.
• How did you feel during this experience, e.g., did you feel challenged by the complexity of the data or confident in your ability to apply bioinformatic knowledge?

How has this experience contributed to your developing practice?

• Identify what learning you can take from this experience regarding the ability to analyse, interpret, and prepare interpretive reports of clinically relevant findings. What strengths did you demonstrate, e.g., systematic use of bioinformatic tools to verify variant calls?
• What skills and/or knowledge gaps were evident, e.g., unfamiliarity with the optimal visualisation tools for complex genomic regions?
• Compare this experience against previous engagement with similar activities – were any previously identified actions for development achieved? Has your practice improved in integrating different types of NGS data to arrive at an interpretation?
• Identify any challenges you experienced, such as needing to seek advice or clarification on scope of practice regarding the reporting of a low-level variant near the assay’s limit of detection, and how you reacted to this.

What will you take from the experience moving forward?

• Identify the actions or ‘next steps’ you will now take to support the assimilation of what you have learnt, including from any feedback you have received, with regards to NGS data analysis and interpretation.
• What will you do differently next time you approach analysis of a case with complex melanoma structural variants, for instance, by proactively reviewing relevant academic literature on the bioinformatic signatures of these specific alterations?
• Do you need to practise any aspect of the activity further, such as running specific variant call algorithms or key learning outcomes related to analysing and interpreting NGS data?

Beyond action

Have you revisited the experiences?

• How have your subsequent experiences of analysing and interpreting NGS data for colorectal, lung and/or melanoma since completing this specific training activity led you to revisit your initial approach or decisions during that activity? For example, how a subsequent case involving rare genomic aberrations or complex artefacts forced you to re-evaluate the rigour of your initial filtering and manual data review during your first attempt at this training activity?
• Considering what you understand about NGS data analysis, bioinformatics tools, and clinical correlation now, were the actions or considerations you identified after your initial reflection on this training activity sufficient? How have you since implemented or adapted improvements in your systematic approach to data analysis based on further learning and experiences? For example, how you proactively reviewed and integrated the departmental guidelines on verifying the clinical relevance of genomic findings before proceeding to reporting.
• Has discussing challenging NGS data sets or the influence of data artifacts on final interpretation with colleagues, peers, or supervisors changed how you now view your initial experience in this training activity? For example, how professional storytelling with a senior colleague about a difficult case involving a low-level variant near the limit of detection refined your understanding of the critical nature of verifying genomic aberrations against technical quality metrics?

How have these experiences impacted upon current practice?

• How has the learning from this initial training activity, in combination with subsequent experiences, contributed to your overall confidence and competence in analysing and interpreting NGS data for these cancer types, particularly in preparing for assessments like Direct Observations of Practical Skills (DOPS)? For example, how your accumulated ability in handling complex data sets and applying bioinformatics tools now enables you to confidently demonstrate the steps required to perform tumour genotype analysis using bioinformatic pipelines during a DOPS assessment?
• How has reflecting back on this specific training activity, combined with everything you’ve learned since, shaped your current approach to NGS analysis? How does this evolved understanding help you identify when something is beyond your scope of practice or requires escalation? For example, how your evolved approach means you now routinely seek advice immediately when faced with complex genomic rearrangements or novel data artifacts that cannot be resolved using routine departmental tools?
• Looking holistically at your training journey, how has this initial experience, revisited with your current perspective, contributed to your development in meeting the learning outcomes related to analysing, interpreting, and preparing interpretive reports of clinically relevant findings?

Relevant learning outcomes

#	Outcome
# 3	Outcome Analyse, interpret and prepare interpretive reports of clinically relevant findings for patients with colorectal and lung cancer, and melanoma.
# 4	Outcome Evaluate the clinical significance of variants identified for colorectal and lung cancer, and melanoma using a range of bioinformatics tools following best practice guidelines.
# 5	Outcome Interpret the bioinformatic and NGS quality metrics in relation to assay performance and EQA.