TOTAL HEALTH · TIER 2 COMPREHENSIVE REVIEW

Welcome, Jane

A clear starting point for the next decision

You have already navigated years of treatment and several important turns in your cancer journey. This review brings the current clinical picture, the new molecular finding, and the decisions ahead into one place so you and your treating team can examine them carefully.

The goal is not to replace your oncologist or prescribe a treatment. It is to make the evidence, the uncertainties, and the questions that matter now easier to see.

PATIENTJane Doe fictionalDIAGNOSISMetastatic EGFR-mutant lung adenocarcinomaCONSULTATIONAugust 2026

Important: This prototype is educational and does not provide medical advice. Results are intended to support conversations with a licensed treating team.

PLAIN TEXT SUMMARY

YOUR CANCER REVIEW

WHAT WE FOUND AND WHAT HAPPENS NEXT

This section is written specifically for you. It summarizes, in plain language, where things stand now, what we found in the records reviewed, what those findings may mean, and what we suggest happens next. The detailed clinical review that follows provides the supporting medical information and reasoning for you and your treating oncology team.

Where things stand today

You have a type of lung cancer with a change in a gene called EGFR. This finding helped explain why your cancer responded well to osimertinib for several years. More recently, the cancer has begun growing again, particularly in the liver and bones. This means the cancer is no longer being adequately controlled by osimertinib alone and that a new systemic treatment decision is needed.

What we found

A newer liver biopsy still looks like lung adenocarcinoma. In the tissue that was sampled, there was no evidence that the cancer had changed into a small-cell form of lung cancer, which can sometimes occur after treatment with EGFR-targeted therapy.

The newer molecular testing also reported increased copies of another gene called MET. This may be one way the cancer has become resistant to osimertinib. However, the tissue and blood-based molecular tests do not provide exactly the same strength of signal for MET. We therefore believe this finding deserves careful review before it is used to guide the next treatment choice.

What this means for treatment now

You have reached a point where a new systemic treatment strategy needs to be considered. Current oncology guidelines provide established treatment options for patients at this stage. Your molecular findings may also create additional targeted-treatment or clinical-trial possibilities. The goal is not simply to list every available treatment, but to determine which choices make the most sense in the context of your cancer, prior response to treatment, current health, extent of disease, and treatment goals.

THE PATH FORWARD

What we suggest happens next

1
Clarify the MET finding. The molecular results should be reviewed carefully to determine whether MET is likely to be an important cause of resistance in this cancer.
2
Place the patient within the current guideline-supported treatment pathway. The detailed report identifies where this decision falls in the treatment journey and how current guideline-based care should frame the available choices.
3
Consider whether the patient's individual biology changes the priority among those choices. This includes the molecular findings, pathology, pattern of progression, prior response, performance status, organ function, and treatment goals.
4
Review relevant clinical-trial opportunities. The detailed report includes preliminary trial referral considerations and distinguishes currently recruiting opportunities from trials that are closed or appear less suitable.
5
Bring the assessment back to the treating oncology team. With the patient's authorization, the detailed Total Health review can be shared with the treating physicians so that the findings and suggested next steps can be considered together.

Clinical trials

We identified clinical trials that may be relevant to this cancer and geographic region. Some may be actively recruiting, while others may no longer be enrolling or may not fit the patient's particular molecular findings. Recruitment status, individual eligibility, and site-specific cohort availability must always be confirmed directly with the study site before referral.

If Tier 3 Longitudinal Concierge follow-up is elected, Total Health can continue monitoring potentially applicable clinical trials in the patient's region as new studies open, recruitment or cohort status changes, and the patient's treatment course and molecular profile evolve. Newly relevant opportunities can then be brought back to the patient and treating oncology team for consideration.

What this report does — and does not — mean

This report is intended to help the patient and treating physicians understand the cancer, the current decision point, and the choices that may be available. It does not replace the treating oncology team. Treatment decisions should be made with the clinicians responsible for the patient's care, taking into account the complete medical history, preferences, and circumstances.

Your Situation at a Glance

You are a 62-year-old never-smoker living with metastatic lung adenocarcinoma driven by an EGFR exon 19 deletion. Osimertinib controlled the cancer for several years, including through two limited areas of progression that were treated locally.

The cancer is now growing more broadly in the liver and bones. A May 2026 liver biopsy still showed adenocarcinoma, with no modeled small-cell transformation. Tissue testing reported an acquired MET amplification, a finding that can help explain resistance to EGFR-directed therapy.

There is an important uncertainty: the MET signal was clear in tissue but only low-level or indeterminate in blood. Because that distinction may influence which treatments or trials are reasonable, the report places confirmation of MET status at the top of the next-step list.

You remain active and independent with an ECOG performance status of 1. Mild fatigue and right upper-quadrant discomfort are present, while kidney function and blood counts remain broadly preserved. Maintaining function and quality of life is a central decision factor.

The current decision point is progression after long-term osimertinib, with a new tissue MET-amplification signal and a need to compare guideline-supported care, biomarker-directed strategies, and credible trials.

Ask Alice: Why can tissue and blood testing give different MET results?

Questions This Review Addresses

1
What changed after several years of benefit from osimertinib?
2
How confident should we be that MET amplification is driving the current progression?
3
What guideline-supported paths belong in the discussion now?
4
Which biomarker-directed or investigational strategies are plausible—and what must be verified first?
5
How should daily function, symptoms, geography, and quality-of-life goals shape the choice?

Understanding Your Cancer

How the cancer is behaving now

The original EGFR exon 19 driver remains detectable, which means the cancer still carries the biology that made osimertinib effective. The new MET amplification is modeled as an acquired resistance mechanism: a second growth signal may now be helping tumor cells bypass EGFR blockade.

The absence of EGFR C797S and the liver biopsy's continued adenocarcinoma appearance narrow—but do not eliminate—the range of possible resistance mechanisms. The report therefore treats MET as a strong lead that still deserves careful confirmation.

✣ What Makes Your Cancer Unique

FOUNDING DRIVER

EGFR exon 19 deletion has persisted from diagnosis through progression.

ACQUIRED SIGNAL

MET amplification was reported in the liver tissue sample after progression.

CO-ALTERATION

TP53 remains detectable and may reflect more complex tumor biology.

TISSUE / BLOOD DISCORDANCE

Plasma ctDNA showed only a low-level or indeterminate MET signal, so orthogonal review matters.

IMMUNE BIOMARKERS

PD-L1 TPS 5%, low tumor mutational burden (4–5 mut/Mb), and microsatellite-stable disease.

PERSONAL CONTEXT

ECOG 1, preserved independence, and a stated priority to maintain function and quality of life.

Assessment of Current Treatment

Osimertinib delivered meaningful, durable control beginning in May 2022. Continuing it through isolated progression while using local radiation was coherent with the disease pattern at those earlier decision points. The April–July 2026 imaging pattern is different: progression is now systemic, so the next conversation must address a new systemic strategy.

Ask Alice: Does finding MET amplification mean osimertinib stopped working completely?

Compare the Paths in Front of You

The mock source report does not select a single regimen. It organizes three decision pathways for the treating team to compare after the MET result is clarified.

CURRENT DECISION

Guideline-supported systemic care

Established pathway

Strongest near-term certainty

BIOMARKER PATH

MET-directed strategy

Confirmation-dependent

Highest biologic specificity

INVESTIGATIONAL

Clinical-trial evaluation

Eligibility-dependent

Requires live verification

Explore Each Path

Current decisionGuideline-supported systemic care

In Jane's case: A standard post-osimertinib systemic pathway can be discussed now while the molecular finding is reviewed. The exact regimen belongs to the treating oncologist.

Show full details

Why it belongs in the conversation

Systemic progression in the liver and bone means that local therapy alone is unlikely to address the full disease burden. Established post-progression care provides the clearest benchmark against which more specialized options should be compared.

What should shape the choice

Current ECOG 1 function and the goal of maintaining independence.
Mildly rising liver enzymes and alkaline phosphatase in the setting of liver progression.
Prior treatment tolerance, expected toxicity, travel burden, and treatment schedule.

What this report does not do

It does not name a single preferred regimen, dose, or schedule. That requires the full current record, live guideline review, and the treating team's judgment.

Biomarker pathMET-directed strategy

In Jane's case: The tissue result creates a biologically credible path, but confidence in the MET finding and access to an appropriate strategy must be established before relying on it.

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Why it belongs in the conversation

Acquired MET amplification is a recognized modeled bypass mechanism in EGFR-mutant lung cancer after EGFR-directed therapy. The liver biopsy was obtained at the time of systemic progression, making the timing clinically relevant.

What needs confirmation

Obtain the complete tissue report, including assay method, copy-number result, and interpretation threshold.
Consider pathology or molecular-tumor-board review and, if useful, orthogonal confirmation.
Reconcile the tissue result with the low-level or indeterminate plasma finding.

Key uncertainty

A tissue–plasma difference does not automatically invalidate either result. Tumor shedding, sampling location, assay sensitivity, and heterogeneity can all contribute.

InvestigationalClinical-trial evaluation

In Jane's case: A live trial screen may reveal options that combine EGFR-directed treatment, MET-directed treatment, antibody-drug conjugates, or other strategies—but the mock matches are preliminary.

Show full details

Why it belongs in the conversation

The current profile has several elements commonly used for cohort assignment: metastatic nonsquamous NSCLC, EGFR exon 19 deletion, prior osimertinib, tissue MET amplification, and ECOG 1.

What must be verified

Recruitment status, active site, cohort availability, and geographic feasibility.
Prior-line limits, measurable-disease rules, washout windows, and organ-function criteria.
Whether the MET finding is required, allowed, or exclusionary for the specific cohort.

Practical tradeoff

Trials may offer biological fit but introduce uncertainty, extra visits, travel, screening procedures, and the possibility of ineligibility after review.

Clinical Status & Daily-Life Factors

The next plan should be judged not only by tumor biology, but also by how it fits Jane's current health and priorities.

FUNCTION

ECOG 1

Active and independent, with some limitation in strenuous activity.

SYMPTOMS

Mild, present

Fatigue and right upper-quadrant discomfort; no resting shortness of breath.

ORGAN FUNCTION

Broadly preserved

Creatinine remains 0.8–0.9 mg/dL; blood counts are adequate in the modeled record.

LIVER TREND

Needs attention

AST, ALT, and alkaline phosphatase rose modestly as hepatic disease progressed.

Modeled laboratory trend
Test	May 2026	Jun 2026	Jul 2026
Hemoglobin	12.1	11.8	11.6 g/dL
ANC	3.8	4.1	4.4 ×10⁹/L
Platelets	248	265	281 ×10⁹/L
Creatinine	0.8	0.8	0.9 mg/dL
AST / ALT	31 / 28	38 / 34	44 / 41 U/L
Alkaline phosphatase	112	138	166 U/L

Ask Alice: Which health factors usually affect treatment eligibility and daily routine?

Your Cancer Journey

MAR 2022

Presentation

Left upper-lobe lung mass with liver and bone involvement.

APR 2022

Diagnosis and profiling

Lung adenocarcinoma; EGFR exon 19 deletion identified.

MAY 2022

Osimertinib started

Targeted therapy produced a durable initial response.

JUL 2022

Partial response

Thoracic and metastatic disease decreased on imaging.

FEB–MAR 2024

Iliac oligoprogression

A limited bone site was treated with SBRT while osimertinib continued.

OCT–NOV 2025

Solitary liver progression

Local liver-directed radiation was completed.

APR–MAY 2026

Systemic progression

Multiple liver lesions and increasing bone disease; liver biopsy confirmed adenocarcinoma and tissue testing reported acquired MET amplification.

JUL 2026

Current decision point

Further hepatic progression with relatively stable thoracic disease; a new systemic strategy is needed.

Trials Matching Your Profile

These entries reproduce the preliminary referral considerations in the attached mock report. They are not verified recommendations, and statuses can change.

Preliminary high-interest matchNCT07535437

Ivonescimab with Dato-DXd or osimertinib

Memorial Sloan Kettering · New York / New Jersey

Recruiting in the mock source

Confirm the exact cohort, prior-treatment requirements, organ-function criteria, and current site status before referral.

Why it was included

The modeled diagnosis, EGFR history, prior osimertinib, and current performance status create a plausible initial match. The protocol must still be checked line by line.

Mechanistically relevantNCT03778229

SAVANNAH: osimertinib with savolitinib

Biologic context only

Active, not recruiting in the mock source

Included because EGFR-driven disease with acquired MET amplification matches the biologic question, but it is not presented as an open option.

Why it was included

The study directly addresses an EGFR/MET resistance context and helps frame the biology, even though the mock source lists it as not recruiting.

Unlikely fitNCT03755102

Dacomitinib with or without osimertinib

Not an active referral option

Completed in the mock source

The modeled MET finding may conflict with eligibility, and the study status does not support referral.

Why it was included

It appears in the source inventory but is retained mainly to show why a molecular or status mismatch can rule a study out.

Likely low fitNCT06067776

Osimertinib, cetuximab, and tucatinib

UC Davis listed in the mock source

Status and site require reverification

A significant MET alteration may be exclusionary. Verify the current protocol and site activity directly.

Why it was included

It is geographically identifiable in the mock source, but the MET alteration may make the modeled case a poor fit.

Trial eligibility is never established by a report alone. A research coordinator and the treating team must verify the current protocol, cohort, site, and complete medical record.

Ask Alice: What should I ask a trial coordinator before traveling for screening?

Questions for Your Doctor

1
Can we review the full MET result—including copy number, assay method, and the laboratory's threshold for amplification?
2
Would you recommend pathology or molecular-tumor-board review to reconcile the tissue and blood results?
3
What is the strongest standard-care benchmark at this point, and what benefit and toxicity should we expect?
4
If the MET finding is confirmed, which biomarker-directed approaches are realistically available to me?
5
Which trial should be verified first, and could your team contact the site before I travel?
6
How will each path affect my energy, independence, appointment burden, and time at home?

Clinical Detail & Source Review

Open any section for the supporting clinical detail used in this prototype.

Pathology

Initial biopsy: Lung adenocarcinoma; TTF-1 and Napsin A positive, p40 negative.
PD-L1: Tumor proportion score 5%.
Progression biopsy: Liver adenocarcinoma compatible with lung primary; no modeled small-cell transformation.

Molecular and genomic profile

Finding	Initial	Progression
EGFR exon 19 deletion	Detected	Persistent
TP53	Detected	Persistent
MET amplification	Not reported	Acquired tissue signal
EGFR C797S	Not detected	Not detected
TMB / MSI	4 mut/Mb · stable	5 mut/Mb · stable

May 2026 plasma ctDNA: EGFR and TP53 detected; MET low-level or indeterminate; no other clearly actionable modeled finding.

Radiographic disease course

Mar 2022: Baseline thoracic primary with liver and bone metastases.
Jul 2022: Partial response after osimertinib.
Feb 2024: Limited iliac progression.
Oct 2025: Solitary liver progression.
Apr–Jul 2026: Multiple liver lesions and increased bone disease, followed by further hepatic progression with relatively stable thoracic disease.

Treatment history and response

Osimertinib: May 2022 to present in the mock record; durable initial control, then limited and later systemic progression.
Iliac SBRT: March 2024 for oligoprogressive bone disease.
Liver radiation: November 2025 for a solitary hepatic site.

Germline and familial considerations

No pathogenic germline finding is modeled in the supplied report. Family-history information should still be confirmed with the treating team, and germline testing should follow standard clinical indications rather than this prototype.

Limitations and information gaps

The patient, clinical data, dates, and trial-referral considerations are fictional.
The complete original molecular assay files and pathology slides were not independently reviewed.
Trial status, cohort availability, site activity, and eligibility require live verification.
The report does not replace current guidelines, clinician judgment, or a full medical evaluation.
Any treatment decision must account for the complete record, comorbidities, medications, preferences, and real-time clinical status.

Review attribution and source inventory

Prototype structure: Total Health Tier 2 comprehensive review, mock version 4. Modeled sources include oncology notes, pathology summaries, tissue and plasma molecular reports, imaging summaries, treatment history, laboratory trends, guideline references, and a preliminary clinical-trial screen.

Your Action Items

What happens next

1
Clarify the MET result. Gather the full tissue report and discuss assay details, pathology review, and whether orthogonal confirmation would change a decision.
2
Place the case in the current guideline pathway. Ask the treating oncologist to define the standard-care benchmark after systemic progression on osimertinib.
3
Compare the three paths explicitly. Review expected benefit, uncertainty, toxicity, visit burden, and quality-of-life impact for standard, biomarker-directed, and investigational approaches.
4
Verify the most credible trial first. Confirm recruitment, cohort, site, key eligibility rules, and travel practicality before any referral.
5
Bring the review to the treating team. Use the six questions above to decide what additional information is needed and who will own each follow-up.

Important disclaimer: This fictional prototype draws on modeled medical literature, guidelines, and clinical information, but it does not provide medical advice or treatment recommendations. Always consult qualified healthcare professionals for medical decisions.