Haematological Malignancies 2 —
Training activity: 9

Details

Interpret and draft a clinical report for NGS for the diagnosis and treatment decisions of lymphoid disorders

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 interpreting complex NGS data and drafting clinical reports for lymphoid disorders.
• Consider how the learning outcomes apply, specifically in relation to report preparation, interpreting somatic variants and clonality, and ensuring collaboration with relevant specialties.
• Discuss with your training officer to gain clarity of what is expected of you in relation to expectations for integrating multiple genomic alterations and classifying variants of unknown significance.

What is your prior experience of this activity?

• Think about your knowledge of NGS technology, bioinformatics tools, and interpretation principles for lymphoid malignancies.
• Consider possible challenges you might face during the activity, such as interpreting complex NGS data, dealing with multiple concurrent variants, or robustly classifying variants of unknown significance (VUS).
• 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 the interpretation requires VUS classification or if conflicting data arises between NGS and other molecular techniques (e.g., clonality assays).
• Acknowledge how you feel about interpreting and reporting complex, high-throughput genomic data.

What do you anticipate you will learn from the experience?

• Consider the specific skills you want to develop, such as navigating NGS analysis software, interpreting variant calls, and efficiently integrating complex findings into a clear clinical report.
• Identify the specific insights you hope to gain into the wide spectrum of genomic alterations found in lymphoid malignancies and their clinical significance as revealed by NGS.

What additional considerations do you need to make?

• Consult actions identified following previous experiences of NGS data analysis and complex variant interpretation (e.g., in S-CG-S1).
• Identify important information you need to consider before embarking on the activity, such as the specific gene panel or assay used and any associated quality control metrics which impact data reliability.

In action

Is anything unexpected occurring?

• Are you noticing anything surprising or different from what you anticipate whilst interpreting complex Next-Generation Sequencing (NGS) data for lymphoid disorders?
• Are you encountering situations such as:
  • NGS findings that point towards an alternative diagnosis?
  • Multiple concurrent variants requiring complex integration for risk assessment?
  • Difficulty classifying a variant of unknown significance?
  • Surprising variant combinations or patterns that challenge routine interpretation?

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 adapting or changing your approach to analysis by immediately checking COSMIC or other databases for novel variant pathogenicity?
• Consider the steps you are taking in the moment, such as seeking input from a bioinformatician to verify the quality of a low allele frequency variant call.
• How are you feeling in that moment? For instance, are you finding it difficult to integrate complex multi-variant findings? Is it affecting your confidence in writing a clear and concise report?

What is the conclusion or outcome?

• Identify how you are working within your scope of practice. For example, are you successfully navigating the bioinformatic data and prioritising variants? Or are you needing support because the interpretation requires classification of findings of complex variants of unknown significance that fall outside routine guidelines?
• What are you learning as a result of the unexpected development? For example, are you gaining insight into the wide spectrum of genomic alterations and interpretative challenges specific to lymphoid disorders revealed by NGS?

On action

What happened?

• Begin by summarising the key steps you took when interpreting the NGS data and drafting the clinical report for the lymphoid disorder case(s).
• Consider specific events, actions, or interactions which felt important, such as the key findings from the NGS, the specific genes or variants identified, and how the NGS results integrated with other diagnostic information (e.g., cytogenetics or immunophenotype).
• Include any ‘reflect-in-action’ moments where you had to adapt to the situation as it unfolded, for instance, immediately seeking consultation when faced with a variant of unknown significance that complicated the final diagnostic conclusion, requiring clarification on its potential pathogenicity.
• How did you feel during this experience, e.g., did you feel challenged by the data volume but focused on ensuring clinical relevance?

How has this experience contributed to your developing practice?

• Identify what learning you can take from this experience regarding NGS interpretation. What strengths did you demonstrate, e.g., skill in utilising bioinformatics tools to analyse the data?
• What skills and/or knowledge gaps were evident, e.g., unfamiliarity with rare somatic mutations specific to certain T-cell lymphomas?
• Compare this experience against previous engagement with similar activities – were any previously identified actions for development achieved? Has your practice improved in your understanding of using NGS for lymphoid disorders and ability to interpret NGS variants and their clinical significance?
• Identify any challenges you experienced, such as needing to seek advice or clarification on scope of practice regarding the requirement to recommend follow-up NGS or other non-routine testing based on initial findings, 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 enhancing your NGS interpretation and reporting skills.
• What will you do differently next time you approach NGS interpretation, for instance, by proactively reviewing multiple variant databases (e.g., ClinVar) before commencing the report drafting process?
• Do you need to practise any aspect of the activity further, such as reviewing multi-gene analysis interpretation or key knowledge outcomes related to the role of NGS in diagnosis and treatment decisions of lymphoid disorders?

Beyond action

Have you revisited the experiences?

• How have your subsequent experiences of interpreting and reporting complex NGS panels for lymphoid disorders since completing this specific training activity led you to revisit your initial approach or decisions during that activity? For example, how an instance where a subsequent T-cell lymphoma case revealed multiple sub clonal variants with unclear pathogenicity forced you to re-evaluate the diligence of your classification of variants of uncertain significance during your first attempt at this training activity?
• Considering what you understand about NGS data interpretation, multi-variant analysis, and reporting standards 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 bioinformatic analysis workflow and use of genomic databases based on further learning and experiences? For example, how you proactively reviewed and integrated specialist literature for reporting variants in specific rare lymphoid malignancies?
• Has discussing challenging findings of variants of uncertain significance or the impact of misclassified somatic variants on therapeutic choice 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 report where a critical therapeutic target variant was initially overlooked refined your understanding of the critical nature of systematic variant prioritisation in NGS interpretation?

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 NGS interpretation and reporting for lymphoid disorders, particularly in preparing for assessments like DOPS on interpreting NGS results? For example, how your accumulated ability in integrating multi-variant results for risk assessment now enables you to confidently interpret a complex lymphoid NGS case 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 lymphoid NGS reporting? 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 the NGS results conflict with previous molecular or cytogenetic findings?
• Looking holistically at your training journey, how has this initial NGS reporting experience, revisited with your current perspective, contributed to your development in analysing, interpreting, and drafting reports and recognising when a situation is beyond your scope of practice?

Relevant learning outcomes

#	Outcome
# 4	Outcome Analyse, interpret and prepare interpretive reports for common haematological malignancies, including results for somatic variants, clonality, and somatic hypermutation.
# 5	Outcome Interpret the associated IQC and EQA of the laboratory tests for investigation of haematological malignancies.
# 6	Outcome Practice with the relevant specialties for the diagnosis, monitoring and management of haematological malignancies.