MPNST with adverse molecular / clinical features: biallelic CDKN2A/B loss (>80% high-grad...
Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.
| ID | RF-MPNST-HIGH-RISK-BIOLOGY |
|---|---|
| Тип | Тривожна ознака |
| Статус | переглянуто 2026-04-27 | очікує клінічного підпису |
| Хвороби | DIS-MPNST |
| Джерела | SRC-NCCN-SARCOMA SRC-ONCOKB |
Походження тривожної ознаки
| Визначення | MPNST with adverse molecular / clinical features: biallelic CDKN2A/B loss (>80% high-grade MPNST; defines transition from atypical neurofibroma to malignancy), TP53 mutation (~50% high-grade, prognostically poor), NF1 germline loss-of-function (~50% MPNST cases — NF1-associated, worse prognosis than sporadic), tumor size >10 cm, or post-radiation MPNST (10% — biologically aggressive) — each shifts toward intensified neoadjuvant doxorubicin + ifosfamide and aggressive surgical margins. |
|---|---|
| Клінічний напрям | intensify |
| Категорія | high-risk-biology |
Логіка спрацьовування
{
"any_of": [
{
"finding": "BIO-CDKN2A",
"value": "biallelic_loss"
},
{
"finding": "BIO-TP53-MUTATION",
"value": "positive"
},
{
"finding": "nf1_germline_loss_of_function",
"value": true
},
{
"comparator": ">",
"finding": "primary_tumor_size_cm",
"threshold": 10
},
{
"finding": "post_radiation_mpnst",
"value": true
}
],
"type": "biomarker"
}
Нотатки
CDKN2A/B biallelic loss is the defining genomic event differentiating high-grade MPNST from atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP) per recent consensus criteria. TP53 mutations co-occur in high-grade — confer chemoresistance signal. NF1-associated MPNST has worse 5-yr OS (~30%) vs sporadic (~50%). Post-radiation MPNST (latency 10-20 yr) — biologically aggressive, often unresectable due to RT field constraints. Size >10 cm is Joensuu prognostic threshold. Intensification: neoadjuvant AI (doxorubicin + ifosfamide) followed by R0 resection + adjuvant RT — improves limb salvage rate. Selumetinib has activity in NF1- related plexiform NF (SPRINT) but data in frank MPNST limited.
Де використовується
У YAML-корпусі не знайдено зворотних посилань.