{
    "info": {
        "nct_id": "NCT04988191",
        "official_title": "The Efficacy and Safety of Toripalimab Combined With Bevacizumab and Chemotherapy as Neoadjuvant Therapy in Patients With Advanced MSI-H or dMMR Colorectal Cancer: an Open-label, Multicenter, Single-arm, Phase Ib/II Study",
        "inclusion_criteria": "1. Histologically confirmed colorectal adenocarcinoma meeting any of the following criterion: a) T3-4 resectable rectal cancer; b) T1-2 rectal cancer located within 12 cm from the anal verge and refusing direct surgery or radiation therapy; c) T4a-b resectable colon cancer.\n2. Microsatellite instability-high (MSI-H) or DNA mismatch repair-deficient (dMMR).\n3. Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria and haven't received any local treatment.\n4. Eastern Cooperative Oncology Group (ECOG) 0-1.\n5. Fully aware of this study and having signed informed consent.\n6. Age 18 to 75 years old without gender limitation.\n7. Good compliance.\n8. Absolute neutrophil count ≥1500/mm3, platelet ≥100,000/mm3, Hb ≥10g/dl, serum creatinine ≤1.5 times ULN, creatinine clearance rate ≥50mL/min, ALT and AST ≤2.5 times ULN, INR or aPTT ≤1.5 times ULN (INR ≤2 times ULN and aPTT in normal range for patients who are on prophylactic anticoagulant therapy within 14 days before study treatment), total bilirubin level ≤2 times ULN (within 7 days before study treatment).\n9. Women of childbearing age should confirm that serum pregnancy test is negative and agree to use effective contraceptive methods during study treatment and the following 60 days.\nHealthy volunteers allowed\nMust have minimum age of 18 Years\nMust have maximum age of 75 Years",
        "exclusion_criteria": "1. Previously received anti-PD1 or anti-PDL1 or anti-PDL2 or anti-CTLA4.\n2. Uncontrolled active bleeding from the primary tumor or intestinal obstruction.\n3. Contraindications of bevacizumab or irinotecan.\n4. Hypersensitivity to other monoclonal antibodies.\n5. Any active, known or suspected autoimmune disease.\n6. Uncontrolled pleural effusion, pericardial effusion, or ascites to a moderate or greater extent.\n7. History of one of the following dieases: idiopathic pulmonary fibrosis, organized pneumonia (eg. bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia and interstitial pneumonia, or evidence of active pneumonia through enhanced chest CT screening.\n8. Major surgery within 4 weeks before enrollment and haven't fully recovered from the previous surgery.\n9. Active bleeding or abnormal coagulation (aPTT >43s or INR >1.5 times ULN), or having a tendency to bleed or receiving thrombolytic or anticoagulant therapy.\n10. Previously received allogeneic stem cell or parenchymal organ transplantation.\n11. Any significant clinical or laboratory abnormality that the investigator considers to influence the safety assessment, eg. uncontrolled active infection, uncontrolled diabetes, hypertension that cannot be reduced to normal range with monotherapy, grade II or above peripheral neuropathy, congestive heart failure, heart disease (class II or higher) as defined by the New York College of Cardiology, myocardial infarction within 3 months prior to enrollment, unstable arrhythmias, unstable angina pectinis, chronic kidney disease, abnormal thyroid function and previous or co-existing malignancies.\n12. History of uncorrected serum electrolyte disturbances such as potassium, calcium and magnesium.\n13. HIV infection.\n14. Active hepatitis B or hepatitis C.\n15. Pregnancy or lactation period, or unwilling to use contraception during the trial.\n16. With other malignancy within 5 year, except cervical carcinoma in situ, basal or squamous skin cancer, local prostatic carcinoma and ductal carcinoma in situ.\n17. Use corticosteroids (dose of prednisone or similar drugs> 10mg/day) or other immunosuppressive agents within 14 days before enrollment.\n18. Patients with active tuberculosis (TB) who are receiving anti-TB treatment or have received anti-TB treatment within 1 year.\n19. Active infection, or treatment with oral or intravenous antibiotics within the first 2 weeks prior to neoadjuvant therapy, except prophylactic administration.\n20. Anti-infective vaccine (eg. influenza vaccine, varicella vaccine, etc.) injection within 4 weeks before neoadjuvant therapy.\n21. Previous participation in other clinical trials within 4 weeks before neoadjuvant therapy.\n22. Any other disease, metabolic disorder, abnormal physical examination or abnormal laboratory results that may contrainn the use of trial drug, or affect the reliability of study results, or lead to high risk of treatment complications, or affect patient compliance.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Histologically confirmed colorectal adenocarcinoma meeting any of the following criterion: a) T3-4 resectable rectal cancer; b) T1-2 rectal cancer located within 12 cm from the anal verge and refusing direct surgery or radiation therapy; c) T4a-b resectable colon cancer.",
            "criterions": [
                {
                    "exact_snippets": "Histologically confirmed colorectal adenocarcinoma",
                    "criterion": "colorectal adenocarcinoma",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "histologically confirmed"
                        }
                    ]
                },
                {
                    "exact_snippets": "T3-4 resectable rectal cancer",
                    "criterion": "rectal cancer",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "T3-4"
                        },
                        {
                            "requirement_type": "resectability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "T1-2 rectal cancer located within 12 cm from the anal verge and refusing direct surgery or radiation therapy",
                    "criterion": "rectal cancer",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "T1-2"
                        },
                        {
                            "requirement_type": "location",
                            "expected_value": "within 12 cm from the anal verge"
                        },
                        {
                            "requirement_type": "treatment refusal",
                            "expected_value": [
                                "direct surgery",
                                "radiation therapy"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "T4a-b resectable colon cancer",
                    "criterion": "colon cancer",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "T4a-b"
                        },
                        {
                            "requirement_type": "resectability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Microsatellite instability-high (MSI-H) or DNA mismatch repair-deficient (dMMR).",
            "criterions": [
                {
                    "exact_snippets": "Microsatellite instability-high (MSI-H)",
                    "criterion": "microsatellite instability",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "high"
                        }
                    ]
                },
                {
                    "exact_snippets": "DNA mismatch repair-deficient (dMMR)",
                    "criterion": "DNA mismatch repair",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "deficient"
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria and haven't received any local treatment.",
            "criterions": [
                {
                    "exact_snippets": "Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria",
                    "criterion": "measurable disease",
                    "requirements": [
                        {
                            "requirement_type": "criteria",
                            "expected_value": "RECIST 1.1"
                        }
                    ]
                },
                {
                    "exact_snippets": "haven't received any local treatment",
                    "criterion": "local treatment",
                    "requirements": [
                        {
                            "requirement_type": "received",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Eastern Cooperative Oncology Group (ECOG) 0-1.",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) 0-1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Fully aware of this study and having signed informed consent.",
            "criterions": [
                {
                    "exact_snippets": "Fully aware of this study",
                    "criterion": "awareness of study",
                    "requirements": [
                        {
                            "requirement_type": "awareness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "having signed informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Age 18 to 75 years old without gender limitation.",
            "criterions": [
                {
                    "exact_snippets": "Age 18 to 75 years old",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 18,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 75,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "without gender limitation",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "limitation",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Good compliance.",
            "criterions": [
                {
                    "exact_snippets": "Good compliance.",
                    "criterion": "compliance",
                    "requirements": [
                        {
                            "requirement_type": "quality",
                            "expected_value": "good"
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Absolute neutrophil count ≥1500/mm3, platelet ≥100,000/mm3, Hb ≥10g/dl, serum creatinine ≤1.5 times ULN, creatinine clearance rate ≥50mL/min, ALT and AST ≤2.5 times ULN, INR or aPTT ≤1.5 times ULN (INR ≤2 times ULN and aPTT in normal range for patients who are on prophylactic anticoagulant therapy within 14 days before study treatment), total bilirubin level ≤2 times ULN (within 7 days before study treatment).",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count ≥1500/mm3",
                    "criterion": "absolute neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1500,
                                "unit": "mm3"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "platelet ≥100,000/mm3",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100000,
                                "unit": "mm3"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Hb ≥10g/dl",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 10,
                                "unit": "g/dl"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "serum creatinine ≤1.5 times ULN",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "times ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinine clearance rate ≥50mL/min",
                    "criterion": "creatinine clearance rate",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "mL/min"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ALT and AST ≤2.5 times ULN",
                    "criterion": "ALT and AST levels",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "times ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "INR or aPTT ≤1.5 times ULN",
                    "criterion": "INR or aPTT",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "times ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "INR ≤2 times ULN and aPTT in normal range for patients who are on prophylactic anticoagulant therapy within 14 days before study treatment",
                    "criterion": "INR and aPTT for patients on prophylactic anticoagulant therapy",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "times ULN"
                            }
                        },
                        {
                            "requirement_type": "range",
                            "expected_value": "normal range"
                        }
                    ]
                },
                {
                    "exact_snippets": "total bilirubin level ≤2 times ULN (within 7 days before study treatment)",
                    "criterion": "total bilirubin level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "times ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Women of childbearing age should confirm that serum pregnancy test is negative and agree to use effective contraceptive methods during study treatment and the following 60 days.",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing age",
                    "criterion": "gender and reproductive status",
                    "requirements": [
                        {
                            "requirement_type": "expected gender",
                            "expected_value": "female"
                        },
                        {
                            "requirement_type": "reproductive status",
                            "expected_value": "childbearing age"
                        }
                    ]
                },
                {
                    "exact_snippets": "serum pregnancy test is negative",
                    "criterion": "serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "agree to use effective contraceptive methods during study treatment and the following 60 days",
                    "criterion": "contraceptive use",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "during study treatment and the following 60 days"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 75 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 75 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 75,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Previously received anti-PD1 or anti-PDL1 or anti-PDL2 or anti-CTLA4.",
            "criterions": [
                {
                    "exact_snippets": "Previously received anti-PD1",
                    "criterion": "anti-PD1 treatment",
                    "requirements": [
                        {
                            "requirement_type": "previous treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Previously received ... anti-PDL1",
                    "criterion": "anti-PDL1 treatment",
                    "requirements": [
                        {
                            "requirement_type": "previous treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Previously received ... anti-PDL2",
                    "criterion": "anti-PDL2 treatment",
                    "requirements": [
                        {
                            "requirement_type": "previous treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Previously received ... anti-CTLA4",
                    "criterion": "anti-CTLA4 treatment",
                    "requirements": [
                        {
                            "requirement_type": "previous treatment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Uncontrolled active bleeding from the primary tumor or intestinal obstruction.",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled active bleeding from the primary tumor",
                    "criterion": "active bleeding from the primary tumor",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "intestinal obstruction",
                    "criterion": "intestinal obstruction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Contraindications of bevacizumab or irinotecan.",
            "criterions": [
                {
                    "exact_snippets": "Contraindications of bevacizumab",
                    "criterion": "bevacizumab",
                    "requirements": [
                        {
                            "requirement_type": "contraindications",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Contraindications of ... irinotecan",
                    "criterion": "irinotecan",
                    "requirements": [
                        {
                            "requirement_type": "contraindications",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Hypersensitivity to other monoclonal antibodies.",
            "criterions": [
                {
                    "exact_snippets": "Hypersensitivity to other monoclonal antibodies.",
                    "criterion": "hypersensitivity",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Any active, known or suspected autoimmune disease.",
            "criterions": [
                {
                    "exact_snippets": "active, known or suspected autoimmune disease",
                    "criterion": "autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "active",
                                "known",
                                "suspected"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Uncontrolled pleural effusion, pericardial effusion, or ascites to a moderate or greater extent.",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled pleural effusion",
                    "criterion": "pleural effusion",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled ... pericardial effusion",
                    "criterion": "pericardial effusion",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled ... ascites to a moderate or greater extent",
                    "criterion": "ascites",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Major surgery within 4 weeks before enrollment and haven't fully recovered from the previous surgery.",
            "criterions": [
                {
                    "exact_snippets": "Major surgery within 4 weeks before enrollment",
                    "criterion": "major surgery",
                    "requirements": [
                        {
                            "requirement_type": "time since surgery",
                            "expected_value": {
                                "operator": "<",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "haven't fully recovered from the previous surgery",
                    "criterion": "recovery from previous surgery",
                    "requirements": [
                        {
                            "requirement_type": "recovery status",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Active bleeding or abnormal coagulation (aPTT >43s or INR >1.5 times ULN), or having a tendency to bleed or receiving thrombolytic or anticoagulant therapy.",
            "criterions": [
                {
                    "exact_snippets": "Active bleeding",
                    "criterion": "active bleeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "abnormal coagulation (aPTT >43s or INR >1.5 times ULN)",
                    "criterion": "abnormal coagulation",
                    "requirements": [
                        {
                            "requirement_type": "aPTT",
                            "expected_value": {
                                "operator": ">",
                                "value": 43,
                                "unit": "s"
                            }
                        },
                        {
                            "requirement_type": "INR",
                            "expected_value": {
                                "operator": ">",
                                "value": 1.5,
                                "unit": "times ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "having a tendency to bleed",
                    "criterion": "tendency to bleed",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "receiving thrombolytic or anticoagulant therapy",
                    "criterion": "thrombolytic or anticoagulant therapy",
                    "requirements": [
                        {
                            "requirement_type": "receiving",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Previously received allogeneic stem cell or parenchymal organ transplantation.",
            "criterions": [
                {
                    "exact_snippets": "Previously received allogeneic stem cell ... transplantation.",
                    "criterion": "allogeneic stem cell transplantation",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Previously received ... parenchymal organ transplantation.",
                    "criterion": "parenchymal organ transplantation",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Any significant clinical or laboratory abnormality that the investigator considers to influence the safety assessment, eg. uncontrolled active infection, uncontrolled diabetes, hypertension that cannot be reduced to normal range with monotherapy, grade II or above peripheral neuropathy, congestive heart failure, heart disease (class II or higher) as defined by the New York College of Cardiology, myocardial infarction within 3 months prior to enrollment, unstable arrhythmias, unstable angina pectinis, chronic kidney disease, abnormal thyroid function and previous or co-existing malignancies.",
            "criterions": [
                {
                    "exact_snippets": "uncontrolled active infection",
                    "criterion": "active infection",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled diabetes",
                    "criterion": "diabetes",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hypertension that cannot be reduced to normal range with monotherapy",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "cannot be reduced to normal range with monotherapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "grade II or above peripheral neuropathy",
                    "criterion": "peripheral neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "heart disease (class II or higher) as defined by the New York College of Cardiology",
                    "criterion": "heart disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "class"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "myocardial infarction within 3 months prior to enrollment",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable arrhythmias",
                    "criterion": "arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable angina pectinis",
                    "criterion": "angina pectinis",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "chronic kidney disease",
                    "criterion": "chronic kidney disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "abnormal thyroid function",
                    "criterion": "thyroid function",
                    "requirements": [
                        {
                            "requirement_type": "normality",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "previous or co-existing malignancies",
                    "criterion": "malignancies",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. History of uncorrected serum electrolyte disturbances such as potassium, calcium and magnesium.",
            "criterions": [
                {
                    "exact_snippets": "uncorrected serum electrolyte disturbances such as potassium",
                    "criterion": "serum potassium",
                    "requirements": [
                        {
                            "requirement_type": "correction status",
                            "expected_value": "uncorrected"
                        }
                    ]
                },
                {
                    "exact_snippets": "uncorrected serum electrolyte disturbances such as ... calcium",
                    "criterion": "serum calcium",
                    "requirements": [
                        {
                            "requirement_type": "correction status",
                            "expected_value": "uncorrected"
                        }
                    ]
                },
                {
                    "exact_snippets": "uncorrected serum electrolyte disturbances such as ... magnesium",
                    "criterion": "serum magnesium",
                    "requirements": [
                        {
                            "requirement_type": "correction status",
                            "expected_value": "uncorrected"
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. HIV infection.",
            "criterions": [
                {
                    "exact_snippets": "HIV infection",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Active hepatitis B or hepatitis C.",
            "criterions": [
                {
                    "exact_snippets": "Active hepatitis B",
                    "criterion": "hepatitis B",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "Active ... hepatitis C",
                    "criterion": "hepatitis C",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Pregnancy or lactation period, or unwilling to use contraception during the trial.",
            "criterions": [
                {
                    "exact_snippets": "Pregnancy",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "lactation period",
                    "criterion": "lactation period",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "unwilling to use contraception during the trial",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. With other malignancy within 5 year, except cervical carcinoma in situ, basal or squamous skin cancer, local prostatic carcinoma and ductal carcinoma in situ.",
            "criterions": [
                {
                    "exact_snippets": "other malignancy within 5 year",
                    "criterion": "other malignancy",
                    "requirements": [
                        {
                            "requirement_type": "time since diagnosis",
                            "expected_value": {
                                "operator": "<",
                                "value": 5,
                                "unit": "year"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except cervical carcinoma in situ",
                    "criterion": "cervical carcinoma in situ",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except ... basal or squamous skin cancer",
                    "criterion": "basal or squamous skin cancer",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except ... local prostatic carcinoma",
                    "criterion": "local prostatic carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except ... ductal carcinoma in situ",
                    "criterion": "ductal carcinoma in situ",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Use corticosteroids (dose of prednisone or similar drugs> 10mg/day) or other immunosuppressive agents within 14 days before enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Use corticosteroids (dose of prednisone or similar drugs> 10mg/day)",
                    "criterion": "corticosteroid use",
                    "requirements": [
                        {
                            "requirement_type": "dose",
                            "expected_value": {
                                "operator": ">",
                                "value": 10,
                                "unit": "mg/day"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "other immunosuppressive agents within 14 days before enrollment",
                    "criterion": "immunosuppressive agent use",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 14 days before enrollment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "18. Patients with active tuberculosis (TB) who are receiving anti-TB treatment or have received anti-TB treatment within 1 year.",
            "criterions": [
                {
                    "exact_snippets": "Patients with active tuberculosis (TB)",
                    "criterion": "active tuberculosis (TB)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "receiving anti-TB treatment",
                    "criterion": "anti-TB treatment",
                    "requirements": [
                        {
                            "requirement_type": "current treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "have received anti-TB treatment within 1 year",
                    "criterion": "anti-TB treatment",
                    "requirements": [
                        {
                            "requirement_type": "treatment history",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "year"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "19. Active infection, or treatment with oral or intravenous antibiotics within the first 2 weeks prior to neoadjuvant therapy, except prophylactic administration.",
            "criterions": [
                {
                    "exact_snippets": "Active infection",
                    "criterion": "active infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment with oral or intravenous antibiotics within the first 2 weeks prior to neoadjuvant therapy",
                    "criterion": "antibiotic treatment",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        },
                        {
                            "requirement_type": "prophylactic administration",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "20. Anti-infective vaccine (eg. influenza vaccine, varicella vaccine, etc.) injection within 4 weeks before neoadjuvant therapy.",
            "criterions": [
                {
                    "exact_snippets": "Anti-infective vaccine (eg. influenza vaccine, varicella vaccine, etc.) injection within 4 weeks before neoadjuvant therapy.",
                    "criterion": "anti-infective vaccine injection",
                    "requirements": [
                        {
                            "requirement_type": "time before neoadjuvant therapy",
                            "expected_value": {
                                "operator": "<",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "21. Previous participation in other clinical trials within 4 weeks before neoadjuvant therapy.",
            "criterions": [
                {
                    "exact_snippets": "Previous participation in other clinical trials within 4 weeks before neoadjuvant therapy.",
                    "criterion": "previous participation in other clinical trials",
                    "requirements": [
                        {
                            "requirement_type": "time since last participation",
                            "expected_value": {
                                "operator": "<",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "22. Any other disease, metabolic disorder, abnormal physical examination or abnormal laboratory results that may contrainn the use of trial drug, or affect the reliability of study results, or lead to high risk of treatment complications, or affect patient compliance.",
            "criterions": [
                {
                    "exact_snippets": "Any other disease",
                    "criterion": "other disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "metabolic disorder",
                    "criterion": "metabolic disorder",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "abnormal physical examination",
                    "criterion": "abnormal physical examination",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "abnormal laboratory results",
                    "criterion": "abnormal laboratory results",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [
        {
            "line": "7. History of one of the following dieases: idiopathic pulmonary fibrosis, organized pneumonia (eg. bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia and interstitial pneumonia, or evidence of active pneumonia through enhanced chest CT screening.",
            "criterions": [
                {
                    "exact_snippets": "History of one of the following diseases: idiopathic pulmonary fibrosis",
                    "criterion": "idiopathic pulmonary fibrosis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History of one of the following diseases: ... organized pneumonia (eg. bronchiolitis obliterans)",
                    "criterion": "organized pneumonia",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History of one of the following diseases: ... drug-induced pneumonia",
                    "criterion": "drug-induced pneumonia",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History of one of the following diseases: ... idiopathic pneumonia",
                    "criterion": "idiopathic pneumonia",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History of one of the following diseases: ... interstitial pneumonia",
                    "criterion": "interstitial pneumonia",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "evidence of active pneumonia through enhanced chest CT screening",
                    "criterion": "active pneumonia",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}