Pass on the Positivity

​When I was told I had stage IV oesophageal adenocarcinoma, my kids named the tumour Dave. Black humour helps when life gets sharp. What helped even more was clarity. That’s why I pushed for next-generation sequencing, often abbreviated as “NGS”. It didn’t hand me a miracle. It did something more useful – it turned a foggy battlefield into a map my team and I could actually use.

This post explains what NGS is, how it shapes real decisions, where it falls short, how I picked my provider, and what I’d do if I were in your shoes. I’m not selling miracles or bashing medicine. I’m aiming for clarity and practical steps.

woman doing research while holding equipment
Photographer: National Cancer Institute | Source: Unsplash

What NGS actually is

NGS (next-generation sequencing) is a lab technology that reads all of the DNA or RNA from a cancer sample at once, instead of looking at only one gene at a time. For instance, instead of asking a single yes-or-no question about one gene, NGS can scan dozens or hundreds of genes in one go. It can identify point mutations (small changes in a DNA sequence), fusions (when two genes join together), copy-number changes (when a gene or genes are duplicated or missing), and composite biomarkers like tumour mutational burden (a measure of the number of mutations in tumor DNA) and microsatellite instability (a condition where repetitive DNA sequences become unstable). You’ll also hear the terms “comprehensive genomic profiling” or “biomarker testing.” For a practical explainer: https://www.cancer.gov/about-cancer/treatment/types/biomarker-testing-cancer-treatment

There are two main ways to do this:

There is also then, Whole-genome sequencing (WGS) which is the much bigger tool. Instead of just a panel, WGS reads the entire genome. In the UK, the NHS Genomic Medicine Service and the National Genomic Test Directory make it easier to know who can get which tests and when: https://www.england.nhs.uk/publication/national-genomic-test-directories/ and https://www.england.nhs.uk/genomics/the-national-genomic-test-directory/

Genomics England’s large-scale data show that WGS, combined with clinical data, can refine diagnoses and guide treatment planning in routine care: https://www.genomicsengland.co.uk/news/landmark-national-study-supports-use-of-whole-genome-sequencing-in-standard-cancer-care

Liquid-biopsy pathways are also being introduced in England for specific cancers to speed targeted decisions: https://www.theguardian.com/society/2025/may/29/revolutionary-dna-blood-test-to-offer-thousands-in-england-tailored-cancer-care

man looking at microscope
Photographer: National Cancer Institute | Source: Unsplash

Why I did it

I wanted to know if there were actionable alterations that opened targeted drugs or trials. I wanted to know if my tumour was MSI-high, what my TMB looked like, and how to plan next steps instead of reacting in panic. I also wanted to avoid dead ends. Precision oncology is about matching the mechanism to the human in front of you, not chasing headlines. Frameworks like ESMO’s ESCAT help rank which genomic findings actually change outcomes. Translation: not every mutation you can name is worth chasing: https://www.annalsofoncology.org/article/S0923-7534(19)34179-1/fulltext

Why I chose Astron Health

I looked at multiple routes and companies – Tempus, Foundation Medicine, Caris Life Sciences, Guardant, OncoDNA, Datar Cancer Genetics, and others. I ultimately used Astron Health for two very practical reasons.

  1. Patient-first process
    From the start, Astron treated me as a person, not just a case. I spoke directly with their medical lead (Dr. Padman Vamadevan), not just an admin. They were both kind and practical. They even suggested cheaper options if those made more sense. That approach matters when you’re overwhelmed with choices.
    Astron site: https://www.astron.health/
    About Astron: https://www.astron.health/about-us
    FAQ: https://www.astron.health/faq
  2. In-house interpretation by a doctor
    Most companies will happily take your money for the test; then you have to scramble to find a specialist who can translate the data into a plan. Astron included expert interpretation of the raw NGS output and their report. For me, that meant fewer plates to spin and a far more usable end product. They also had Dr Hari Kuhan on their interpretation panel, whom I was already working with. That continuity reduced noise when I needed less, not more.

Transparency: I now have an Astron affiliate link. I’m not here to push them. I’m recommending Astron because they were the best I found, and they worked for me. If you use my link, it helps cover blog costs. If not, that’s fine. Always use your own judgement and talk to your clinical team.

Link Here: Astron Affiliate Link

​Watch: what NGS is – my story and Astron’s role

If you prefer video to text, here’s a short webinar where we keep it simple. We explain what next-gen sequencing is, how it fits into real-world decisions, and where it sat in my own stage 4 journey. We also touch on why I chose Astron Health – patient-first process and in-house medical interpretation – and how that reduced the noise for me. Watch here: https://youtu.be/WhdREDOx6UE?si=ioE9dOkKEXtWMv3M.

What you will see:

  • What NGS is in plain English – tissue panels, whole-genome sequencing, and liquid biopsy.
  • Where NGS helped me choose and stop choosing – no miracle claims, just clearer decisions.
  • Why Astron stood out in my case – direct access to the medical lead and integrated interpretation.

Transparency note: I now have an affiliate link with Astron. I recommend them because they were the best fit I found, not because of the link. If you choose to use my link it helps cover the costs of keeping this site running. If you prefer to go direct or use another provider, please do. Your case and your clinical team come first.

shallow focus photography of white bottle lot
Photographer: National Cancer Institute | Source: Unsplash

Alternatives to compare – different tools for different jobs

I’m not linked to any of the companies below. I’m listing them so you can see your options and pick what fits your cancer, timing, and what’s available to you.

Comprehensive genomic profiling – tissue and liquid

MRD and recurrence monitoring – different purpose from CGP

Tip: Match the tool to the job. Use CGP to decide what to treat now or at the next line. Use MRD to determine whether the disease is likely present after treatment and when to act.

A green and black background with lines
Photographer: Logan Voss | Source: Unsplash

What NGS can unlock in real life?

white candle in clear glass holder
Photographer: National Cancer Institute | Source: Unsplash

Where NGS falls short

  1. Some tumours don’t yield easy targets.
    Oesophageal adenocarcinoma often shows TP53 mutations and chromosomal instability across several genes: ERBB2, CDKN2A, SMAD4, ARID1A, and others. Outside HER2-positive disease, there may be fewer clear targets. Information without an obvious drug is still useful, but set expectations: https://www.nature.com/articles/nature20805, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428370/ , and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11026501/
  2. Variants of unknown significance
    You will likely see VUS. Ask that your report follow AMP-ASCO-CAP standards and clearly separate clinically actionable from “interesting.” Standards overview: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081216/ and PubMed entry: https://www.ncbi.nlm.nih.gov/pubmed/27993330
  3. Consent and data choices
    In the NHS, genomic testing has a proper consent workflow. It covers what’s tested, data sharing, and how extra findings are handled. It’s good practice, not red tape: https://www.genomicseducation.hee.nhs.uk/supporting-the-nhs-genomic-medicine-service/requesting-whole-genome-sequencing-information-for-clinicians/ and https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/incidental-findings/
  4. Turnaround and tissue quality
    NGS takes time, and poor samples can fail. Plan biopsy handling upfront to avoid decalcified bone samples that won’t sequence well. A practical primer on tissue stewardship: https://www.jnjprecisionmedicine.com/pdfs/PM-Biomarker-Testing-Challenges-Opportunities-and-the-MDT-Digital-Chapter.pdf
  5. Predictive markers are NOT perfect.
    PD-L1 and TMB shift probabilities. They do not guarantee a response. Keep the nuance in view: https://www.nature.com/articles/s41591-024-03398-5
black wooden framed glass window
Photographer: Vikas Gurjar | Source: Unsplash

How NGS shaped my path

NGS gave me a plan. It confirmed what not to chase, highlighted what to monitor, and framed trial options to line up early. It did not replace chemo or immunotherapy. It sat alongside them – with microbiome care, nutrition, strength work, sleep, and stress control. Not a miracle, but a map.

A field guide you can take to the clinic

1) Eligibility and timing

2) Test type

  • For me, is tissue NGS or liquid biopsy more appropriate first, and why
  • If liquid biopsy is used, which validated assay is available locally, and what will it replace versus complement
    ASCO liquid biopsy overview: https://ascopubs.org/doi/10.1200/EDBK-25-481114

3) Reporting and actionability

4) Turnaround and repeats

5) Immunotherapy context

6) Trials – now, not later

  • Which two or three trials could fit me, and what inclusion criteria should I prepare for
  • Who on the team owns the search

7) Consent, data and family

8) Copies for me

red round fruits on white and blue surface
Photographer: National Cancer Institute | Source: Unsplash

A quick reality check on Oesophageal Adenocarcinoma

If you have OAC like me, set expectations properly. OACs often have TP53 mutations and broad chromosomal instability. HER2 amplification is a meaningful subset, but many OACs won’t fall into a clean drug bucket. That doesn’t make NGS pointless – it makes it a tool for avoiding blind alleys, finding trials, tracking evolution, and moving faster when biology gives you an opening: https://www.nature.com/articles/nature20805, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428370/, and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11026501/

If I were starting today

black and red wooden door
Photographer: CDC | Source: Unsplash

​Building my protocol with Dr Hari Kuhan

On Monday 8 December 2025, I recorded a webinar for Astron with Dr Hari Kuhan. We walked through how we built my treatment protocol step by step, and how Hari used the Astron and Datar reports to inform off-label medications alongside standard care. We tried to keep it practical – what the reports actually said, what we did next, and what we chose not to do. Link will be added here once published.

Final thought

NGS didn’t make my cancer simple. It made it legible. It helped my team pick the right fights and stop shadow-boxing the wrong ones. If you’re reading this in a kitchen at midnight, you’re allowed to ask for clarity. You’re allowed to ask for tests that change decisions. Pair precision with patience – one informed step at a time.

References and further reading

  1. National Genomic Test Directories – NHS England: https://www.england.nhs.uk/publication/national-genomic-test-directories/
  2. About the National Genomic Test Directory: https://www.england.nhs.uk/genomics/the-national-genomic-test-directory/
  3. Genomics England – WGS in standard cancer care: https://www.genomicsengland.co.uk/news/landmark-national-study-supports-use-of-whole-genome-sequencing-in-standard-cancer-care
  4. NCI – Biomarker testing for cancer treatment: https://www.cancer.gov/about-cancer/treatment/types/biomarker-testing-cancer-treatment
  5. ASCO Educational Book – liquid biopsy overview: https://ascopubs.org/doi/10.1200/EDBK-25-481114
  6. Clinical review – ctDNA in practice: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10813828/
  7. NHS liquid biopsy rollout – news coverage: https://www.theguardian.com/society/2025/may/29/revolutionary-dna-blood-test-to-offer-thousands-in-england-tailored-cancer-care
  8. ESMO ESCAT scale: https://www.annalsofoncology.org/article/S0923-7534(19)34179-1/fulltext
  9. Oesophageal adenocarcinoma genomics – TCGA: https://www.nature.com/articles/nature20805
  10. Oesophageal adenocarcinoma – genomic reviews: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428370/ and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11026501/
  11. AMP-ASCO-CAP somatic variant standards: https://www.ncbi.nlm.nih.gov/pubmed/27993330 and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081216/
  12. NHS Genomics Education – WGS requesting info and incidental findings: https://www.genomicseducation.hee.nhs.uk/supporting-the-nhs-genomic-medicine-service/requesting-whole-genome-sequencing-information-for-clinicians/ and https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/incidental-findings/
  13. Astron Health: https://www.astron.health/, https://www.astron.health/about-us, and https://www.astron.health/faq
  14. Tempus – genomic profiling: https://www.tempus.com/oncology/genomic-profiling/
  15. Foundation Medicine – FoundationOne CDx and portfolio: https://www.foundationmedicine.com/test/foundationone-cdx and https://www.foundationmedicine.com/portfolio
  16. Caris Life Sciences – MI Profile and rationale: https://www.carislifesciences.com/physicians/physician-tests/mi-profile/ and https://www.carislifesciences.com/why-order-molecular-profiling/
  17. Guardant Health – EU site and product pages: https://guardanthealth.eu/ and https://guardanthealth.com/products/tests-for-patients-with-early-and-advanced-stage-cancer/
  18. OncoDNA – OncoDEEP and CGP solutions: https://oncodna.com/article/solid_tumor_cgp_oncodeep_tso500/ and https://oncodna.com/for-laboratories/
  19. NeoGenomics – oncology solutions and PanTracer LBx: https://www.neogenomics.com/providers/oncology-solutions/ and https://ir.neogenomics.com/news-events/press-releases/detail/305/neogenomics-launches-pantracer-lbx-expanding-access-to-comprehensive-genomic-profiling-with-liquid-biopsy
  20. Illumina TruSight Oncology 500 – tissue and ctDNA v2: https://emea.illumina.com/products/by-type/clinical-research-products/trusight-oncology-500.html and https://emea.illumina.com/products/by-type/clinical-research-products/trusight-oncology-500-ctdna.html
  21. Datar Cancer Genetics – UK and global: https://uk.datarpgx.com/excta-comprehensive-tumor-analysis and https://datarpgx.com/
  22. MSK-IMPACT – test info and validation: https://www.mskcc.org/msk-impact and https://pmc.ncbi.nlm.nih.gov/articles/PMC5808190/
  23. Natera Signatera – MRD overview and NICE briefing: https://www.natera.com/oncology/signatera-advanced-cancer-detection/ and https://www.nice.org.uk/advice/mib307/chapter/The-technology
  24. Exact Sciences – Oncotype DX: https://www.exactsciences.com/cancer-testing/oncotype-dx-breast-recurrence-score-invasive-ductal

Not medical advice: this blog is educational and based on my experience plus published sources. Always discuss testing and timing with your own clinical team.


Pass on the Positivity

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