Medullary thyroid carcinoma with actionable RET mutation: germline RET M918T (MEN2B — mos...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-MTC-HIGH-RISK-BIOLOGY`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-MTC`
Sources	`SRC-ATA-THYROID-2015` `SRC-NCCN-THYROID-2025`

Red Flag Origin

Definition	Medullary thyroid carcinoma with actionable RET mutation: germline RET M918T (MEN2B — most aggressive, prophylactic thyroidectomy <1 yr), germline RET codon 634 (MEN2A), somatic RET M918T (~25-30% sporadic MTC, more aggressive), or RAS mutation (HRAS / KRAS / NRAS, ~15-20% sporadic, mutually exclusive with RET) — opens selpercatinib / pralsetinib targeted therapy line for advanced disease.
Clinical direction	intensify
Category	high-risk-biology

Trigger Logic

{
  "any_of": [
    {
      "finding": "BIO-RET-M918T",
      "value": "positive"
    },
    {
      "finding": "BIO-RET",
      "value": "germline_men2"
    },
    {
      "finding": "BIO-RET",
      "value": "somatic_mutation"
    },
    {
      "finding": "BIO-HRAS",
      "value": "positive"
    }
  ],
  "type": "biomarker"
}

Notes

RET M918T (MEN2B) = highest-risk MEN syndrome — prophylactic thyroidectomy in first year of life per ATA guidelines. Sporadic MTC with somatic RET M918T (~25-30%) has worse prognosis than RET-wild- type or RAS-mutant. Selpercatinib (LIBRETTO-001/-531; ORR ~70%, PFS ~25 mo in advanced RET-mutant MTC) is now standard 1L for advanced / metastatic RET-mutant MTC. Pralsetinib (ARROW) similar efficacy. RAS- mutant MTC is RET-wild-type and does NOT respond to RET inhibitors — vandetanib (ZETA) or cabozantinib (EXAM) are 1L for these. Comprehensive germline + tumor RET / RAS testing at diagnosis is now standard (NCCN Cat 1 recommendation).

Used By

No reverse references found in the YAML corpus.