Baseline organ dysfunction precluding standard lenvatinib / sorafenib multikinase inhibit...

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

ID	`RF-THYROID-PAPILLARY-ORGAN-DYSFUNCTION`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-THYROID-PAPILLARY`
Sources	`SRC-ATA-THYROID-2015` `SRC-NCCN-THYROID-2025`

Red Flag Origin

Definition	Baseline organ dysfunction precluding standard lenvatinib / sorafenib multikinase inhibitor for RAI-refractory PTC or affecting selective TKI dosing: LVEF <50% (lenvatinib hypertension + cardiac dysfunction), CrCl <30 mL/min (TKI dose adjustment), bilirubin >3× ULN (sorafenib / lenvatinib hepatic clearance), QTc >480 ms (TKI-class QT prolongation), uncontrolled hypertension, or prior fistula / GI perforation (lenvatinib / sorafenib FDA boxed-warning class).
Clinical direction	de-escalate
Category	organ-dysfunction

Trigger Logic

{
  "any_of": [
    {
      "comparator": "<",
      "finding": "lvef_percent",
      "threshold": 50
    },
    {
      "comparator": "<",
      "finding": "creatinine_clearance_ml_min",
      "threshold": 30
    },
    {
      "comparator": ">=",
      "finding": "bilirubin_ratio_to_uln",
      "threshold": 3
    },
    {
      "comparator": ">",
      "finding": "qtc_ms",
      "threshold": 480
    },
    {
      "finding": "uncontrolled_hypertension",
      "value": true
    },
    {
      "finding": "prior_gi_perforation_or_fistula",
      "value": true
    }
  ],
  "type": "lab_value"
}

Notes

Lenvatinib carries severe hypertension (~70% any grade), proteinuria, hand-foot, and rare fistula / GI perforation (FDA boxed warning class). Sorafenib similar profile + hand-foot more pronounced. Selective RET (selpercatinib, pralsetinib) and NTRK (larotrectinib, entrectinib) inhibitors better-tolerated alternatives — preferred when fusion+. Dabrafenib + trametinib for BRAF-mut RAI-refractory PTC has lower hypertension burden than lenvatinib but adds pyrexia + cardiac monitoring. Most PTC patients are LVEF-normal at presentation but develop cardiac dysfunction on chronic multikinase TKI exposure — baseline ECHO + 3-monthly during therapy.

Used By

No reverse references found in the YAML corpus.