Prediction and Evaluation of Anlotinib Treatment Response Using Contrast Enhanced Ultrasound PPGL Patients

Inclusion Criteria:

• 18 years of age or older.
• Provide written informed consent.
• Willing to return to enrolling institution for follow-up.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
• Life expectancy > 3 months.
• Patients diagnosis with pheochromocytoma or paraganglioma will received anlotinibtreatment.
• Laboratory requirements:
• Absolute granulocyte count (AGC) greater than 1.5 x 109/L;
• Platelet count greater than 80 x 109/L;
• Hemoglobin greater than 90g/L;
• Serum bilirubin less than 1.5 x upper limit of normal (ULN);
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) lessthan 2.5 x ULN;
• Serum creatinine less than 1.5 x ULN or creatinine clearance (CCr)≥60ml/min;
• Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ lowerlimit of normal value (50%).

Exclusion Criteria:

• Patients who are allergic to ultrasound contrast agents.
• Any of the following:Pregnant women,Nursing women,Men or women of childbearingpotential who are unwilling to employ adequate contraception.
• Patients who have previously used other anti-vascular targeted drugs, such assunitinib, bevacizumab, endurance, etc.
• Chemotherapy/systemic therapy, radiotherapy, immunotherapy or surgery within 4 weeksprior to kinase inhibitor therapy.
• Patients with another primary malignancy within 5 years prior to starting study drug. Those who have multiple factors that affect oral medications (such as inability to swallow,chronic diarrhea, intestinal obstruction, etc.).
• Patients with known untreated brain metastases are excluded. Patients having a historyof brain metastasis that have been previously irradiated or resected greater than 2months prior to enrollment and are clinically and radiographically stable will beconsidered for enrollment. Patients with brain metastases with symptoms or symptomcontrol for less than 2 months.
• Active or uncontrolled intercurrent illness including, but not limited to
• Patients with unsatisfactory blood pressure control (systolic blood pressure ≥150mmHg, diastolic blood pressure ≥100 mmHg);
• Patients with uncontrolled myocardial ischemia or myocardial infarction,arrhythmia (including QTC≥480ms), and uncontrolled congestive heart failure，grade ≥2（New York Heart Association )
• ongoing or active infection;
• Liver cirrhosis, decompensated liver disease, active hepatitis or chronichepatitis require antiviral treatment;
• Renal failure requires hemodialysis or peritoneal dialysis;
• Have a history of immunodeficiency, including HIV or other acquired or congenitalimmunodeficiency diseases, or a history of organ transplantation;
• Diabetes is poorly controlled (fasting blood glucose (FBG)> 10mmol/L);
• Urine routines suggest that urine protein is ≥++, and the 24-hour urine proteincontent is confirmed to be greater than 1.0 g;
• Patients who have seizures and need treatment;
• Any of the following conditions =< 6 months prior to registration: Cerebrovascularaccident (CVA) or transient ischemic attack (TIA); Serious or unstable cardiacarrhythmia; Pulmonary embolism, untreated deep venous thrombosis (DVT). Received major surgical treatment, open biopsy or obvious traumatic injury within 28 daysbefore enrollment.
• Those who have a history of psychotropic drug abuse and cannot be quit or have mentaldisorders.
• Imaging shows that the tumor has invaded important blood vessels or the investigatorjudges that the tumor is very likely to invade important blood vessels and cause fatalbleeding during the follow-up study.
• Regardless of the severity, patients with any signs of bleeding or medical history;within 4 weeks before enrollment, patients with any bleeding or bleeding event ≥ CTCAEgrade 3, unhealed wounds, ulcers or fractures.
• Patients are using drugs that interact with Anlotinib.