4.2 Individualized Treatment Planning & Molecular Tumor Boards
Key Takeaways
- An individualized plan requires four inputs assembled together: clinical history and goals, pathology and biomarkers, laboratory and organ function, and radiologic disease extent.
- Treatment intent must be named explicitly as curative, adjuvant, neoadjuvant, disease-control, or palliative, because intent determines how much toxicity is acceptable.
- Actionability of a genomic finding is tiered: an on-label matched therapy outranks an off-label or trial-eligible alteration, which outranks a variant of unknown clinical significance.
- Tumor-only sequencing can incidentally reveal a suspected germline variant, which requires confirmatory germline testing and genetic counseling rather than direct action on the tumor report.
- Baseline organ-function testing must be exposure-specific: echocardiography before anthracyclines or HER2-directed therapy, pulmonary function with DLCO before bleomycin, audiometry before cisplatin, and creatinine clearance before renally cleared agents.
4.2 Individualized Treatment Planning & Molecular Tumor Boards
Blueprint focus: ONCC Domain I.B.4 — Individualized treatment planning based on history, pathology/biomarkers, laboratory, and radiologic results. This is the synthesis item on the blueprint: everything from Chapters 2 and 3 converges here into a plan.
The Four Inputs
A treatment plan is not a regimen selected from an algorithm. It is the intersection of four data streams.
1. Clinical history and patient goals. Age and functional status, comorbidity burden, prior antineoplastic exposure and cumulative doses, prior radiation fields, allergies, reproductive plans, social support, transportation, insurance and out-of-pocket exposure, and — most importantly — what the patient is trying to achieve.
2. Pathology and biomarkers. Histologic subtype and grade; immunohistochemistry; predictive biomarkers that select therapy (ER, PR, HER2, PD-L1, EGFR, ALK, BRAF, KRAS G12C, MSI-H/dMMR, NTRK); prognostic biomarkers that estimate outcome independent of therapy (Ki-67, TP53, 17p deletion); and multigene recurrence assays.
3. Laboratory and organ function. Complete blood count, comprehensive metabolic panel, calculated creatinine clearance, hepatic function, tumor markers where validated, hepatitis B and C and HIV serologies before immunosuppressive therapy, pregnancy testing, and pharmacogenomic screens such as DPYD before fluoropyrimidines and UGT1A1 before irinotecan.
4. Radiologic disease extent. Stage, sites of disease, whether disease is resectable, whether an organ is threatened, and — critically — baseline measurements that will later define response.
Step 1: Name the Treatment Intent
Before selecting any drug, state the intent in the chart. This single sentence determines how much toxicity is acceptable.
| Intent | Definition | Toxicity tolerance |
|---|---|---|
| Curative | Eradication of all disease is the goal | High; dose intensity is preserved wherever possible |
| Neoadjuvant | Given before definitive local therapy to downstage, enable organ preservation, and test in vivo sensitivity | High, but must not preclude surgery |
| Adjuvant | Given after definitive local therapy to eradicate micrometastatic disease in a patient with no measurable tumor | Moderate; the patient is already disease-free, so harms weigh heavily |
| Disease control | Incurable disease treated to prolong survival and delay progression | Moderate; balance duration of benefit against quality of life |
| Palliative | Symptom relief is the objective | Low; any regimen that worsens quality of life fails its own purpose |
Adjuvant intent deserves special care because the patient feels well. Every adverse effect is a harm imposed on someone who has no symptoms, which is why absolute benefit — not relative risk reduction — must be the number discussed.
Step 2: The Molecular Tumor Board
Comprehensive genomic profiling generates far more findings than actionable ones. The molecular tumor board exists to convert a sequencing report into a decision. Membership typically includes medical oncology, pathology and molecular pathology, clinical genetics, pharmacy, bioinformatics, clinical research, and the oncology APRN.
Tiering a genomic finding
| Tier | Finding | Action |
|---|---|---|
| Highest actionability | Alteration with an FDA-approved, on-label matched therapy for this tumor type (for example EGFR exon 19 deletion in NSCLC) | Match therapy directly |
| High | Alteration with a tumor-agnostic approval (MSI-H/dMMR, TMB-high, NTRK fusion, BRAF V600E) | Match therapy across histologies |
| Moderate | Alteration approved in a different tumor type, or with compelling trial data | Seek a clinical trial first; off-label use requires justification and payer navigation |
| Low | Alteration of biological interest without clinical data | Do not act; record for future reassessment |
| Not actionable | Variant of uncertain significance | Do not use to select therapy or surgery; reassess as classification evolves |
Two traps the exam likes
- A negative liquid biopsy does not exclude a driver. Circulating tumor DNA has a high positive predictive value but a substantial false-negative rate when a tumor sheds little DNA. A negative plasma result in a patient who has not been tissue-tested must be followed by tissue sequencing.
- A tumor-only report can flag a germline variant. When somatic sequencing reports a BRCA1/2, mismatch repair, or TP53 alteration at a variant allele fraction suggesting germline origin, the correct action is confirmatory germline testing with genetic counseling, not an assumption either way. Somatic and germline findings have different implications for relatives and for risk-reducing surgery.
Step 3: Baseline Organ-Function Testing Matched to Planned Exposure
| Planned exposure | Required baseline | Why |
|---|---|---|
| Anthracycline or HER2-directed therapy | Echocardiogram or MUGA for LVEF | Cumulative and reversible cardiotoxicity respectively |
| Bleomycin | Pulmonary function tests with DLCO | Pulmonary fibrosis is dose-related and irreversible |
| Cisplatin | Audiometry and creatinine clearance | Irreversible high-frequency hearing loss and nephrotoxicity |
| Carboplatin | Creatinine clearance | Calvert dosing depends directly on GFR |
| Fluoropyrimidine | DPYD genotype | Prevents fatal toxicity in deficient patients |
| Irinotecan | UGT1A1 genotype where indicated | Prevents severe neutropenia and diarrhea |
| Rituximab or other B-cell-depleting therapy | Hepatitis B surface antigen and core antibody | Reactivation risk demands prophylaxis |
| Immune checkpoint inhibitor | Thyroid function, cortisol if symptomatic, baseline glucose | Establishes the baseline against which endocrine irAEs are judged |
| Any gonadotoxic therapy | Pregnancy test, fertility discussion | See Section 4.3 |
Step 4: Modify for the Person, Not Only the Tumor
- Renal impairment — substitute carboplatin for cisplatin; adjust or avoid high-dose methotrexate; recalculate all renally cleared doses.
- Hepatic impairment — reduce anthracyclines, vinca alkaloids, and taxanes according to bilirubin.
- Cardiac disease — cap or avoid anthracyclines; monitor LVEF more frequently with HER2-directed therapy; consider anthracycline-free regimens.
- Autoimmune disease — checkpoint inhibitors are not absolutely contraindicated but require explicit risk discussion and rheumatology co-management.
- Reproductive plans — fertility preservation must precede the first gonadotoxic dose, not follow it.
- Practical feasibility — a weekly infusion regimen is not equivalent to an oral regimen for a patient who lives three hours from the infusion center and cannot drive.
Step 5: Document the Plan So It Can Be Executed
A usable plan states the regimen and dose basis, the intent, the number of planned cycles, the response assessment interval and modality, the specific toxicities being monitored and how, the supportive care ordered prospectively (antiemetics, growth factors, prophylaxis), the criteria that would trigger dose reduction or a change of plan, and the patient's stated goals in their own words. Anything less leaves the next clinician guessing.
Comprehensive genomic profiling of a resected pancreatic adenocarcinoma reports a pathogenic BRCA2 alteration at a variant allele fraction of approximately 50%, consistent with possible germline origin. What is the most appropriate next step?
A 68-year-old woman is scheduled to begin adjuvant doxorubicin-based chemotherapy followed by trastuzumab for HER2-positive breast cancer. She has hypertension and takes lisinopril. Which baseline study is essential before the first dose?
A patient with metastatic non-small cell lung cancer has a plasma circulating tumor DNA panel that reports no actionable alterations. Tissue has not yet been sequenced. What should the nurse practitioner recommend?