RET proto-oncogene activating mutation (somatic or germline) in advanced or metastatic me...

Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.

ID	`RF-MTC-RET-MUTANT`
Тип	Тривожна ознака
Статус	переглянуто 2026-05-08 \| очікує клінічного підпису
Хвороби	`DIS-MTC`
Джерела	`SRC-LIBRETTO-531-WIRTH-2024` `SRC-NCCN-THYROID-2025`

Походження тривожної ознаки

Визначення	RET proto-oncogene activating mutation (somatic or germline) in advanced or metastatic medullary thyroid carcinoma (MTC). RET mutations are the defining oncogenic driver of hereditary and sporadic MTC: approximately 25% of sporadic MTC carry somatic RET mutations (M918T in ~50% of these), and hereditary MTC (Multiple Endocrine Neoplasia type 2A/2B, Familial MTC) is driven by germline RET mutations (C634R/W/Y/F in MEN2A; M918T in MEN2B; C611/C620/C630 in FMTC-risk MEN2A kindreds). Total prevalence of RET-mutant MTC: approximately 60-70% when germline + somatic are combined. RET-mutant status is the primary biomarker gate for selpercatinib over cabozantinib/vandetanib as 1L systemic therapy. LIBRETTO-531 (Wirth NEJM 2024, PMID 39133858) demonstrated selpercatinib superior to physician's choice (cabozantinib or vandetanib) in 1L advanced RET-mutant MTC: median PFS not reached vs 16.8 month...
Клінічний напрям	intensify
Категорія	high-risk-biology
Змінює алгоритм	ALGO-MTC-1L

Логіка спрацьовування

{
  "any_of": [
    {
      "finding": "BIO-RET",
      "value": "M918T"
    },
    {
      "finding": "BIO-RET",
      "value": "C634R"
    },
    {
      "finding": "BIO-RET",
      "value": "C634W"
    },
    {
      "finding": "BIO-RET",
      "value": "C634Y"
    },
    {
      "finding": "BIO-RET",
      "value": "C634F"
    },
    {
      "finding": "BIO-RET",
      "value": "C634S"
    },
    {
      "finding": "BIO-RET",
      "value": "C620R"
    },
    {
      "finding": "BIO-RET",
      "value": "C611Y"
    },
    {
      "finding": "BIO-RET",
      "value": "C630R"
    },
    {
      "finding": "ret_mutation_status",
      "value": "positive"
    },
    {
      "finding": "ret_mutation_status",
      "value": "mutant"
    },
    {
      "finding": "ret_mutation_status",
      "value": "detected"
    },
    {
      "finding": "ret_mutation_status",
      "value": "MEN2A"
    },
    {
      "finding": "ret_mutation_status",
      "value": "MEN2B"
    },
    {
      "finding": "ret_germline_mutation",
      "value": "positive"
    },
    {
      "finding": "ret_somatic_mutation",
      "value": "positive"
    }
  ],
  "type": "biomarker_status"
}

Нотатки

W5c RF authoring. Converts free-text `{condition: "RET mutation positive (somatic M918T OR germline MEN2-associated C634/M918T/other)"}` in ALGO-MTC-1L step 1 into a formal RF entity. Clinical rationale: LIBRETTO-531 (Wirth NEJM 2024, PMID 39133858, NCT04211337) enrolled 291 patients with advanced RET-mutant MTC (both somatic and germline variants; all genotypes). Primary endpoint PFS: HR 0.28 (95% CI 0.16-0.48; p<0.001); median PFS NR vs 16.8 months. ORR 69% vs 38% (p<0.001). Grade 3+ AEs 36% vs 55%. All subgroups benefited; M918T (somatic, highest-risk MEN2B) and germline C634x (MEN2A) are both covered by selpercatinib label. Trigger scope: This RF covers all activating RET mutations. The class- level `ret_mutation_status` findings are the primary triggers when individual variant annotation is not available in the patient record; specific variant triggers (M918T, C634R, etc.) are secondary precision matches for when molecular report specifies the codon. This allows the engine to fire on either a structured biomarker status report or a free-text extraction result. Note: RET fusions (distinct from point mutations) driving NSCLC/thyroid PTC are covered by separate RF entities (RF-N...

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Algorithms

ALGO-MTC-1L - ALGO-MTC-1L