@erosolaraijs/cure 2.3.0 → 2.4.0

package/dist/capabilities/clinicalTrialMatchingModule.js

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+/**
+ * Clinical Trial Matching Engine
+ *
+ * ╔═══════════════════════════════════════════════════════════════════════════════╗
+ * ║  CLINICAL TRIAL MATCHING - CONNECTING PATIENTS TO NOVEL THERAPIES            ║
+ * ╠═══════════════════════════════════════════════════════════════════════════════╣
+ * ║  This module provides:                                                        ║
+ * ║  - Biomarker-to-trial mapping                                                ║
+ * ║  - Eligibility criteria assessment                                           ║
+ * ║  - Trial phase and mechanism matching                                        ║
+ * ║  - Geographic and logistical feasibility                                     ║
+ * ║  - Basket, umbrella, and platform trial navigation                           ║
+ * ╚═══════════════════════════════════════════════════════════════════════════════╝
+ */
+// ═══════════════════════════════════════════════════════════════════════════════
+// TRIAL DATABASE (REPRESENTATIVE EXAMPLES)
+// ═══════════════════════════════════════════════════════════════════════════════
+export const TRIAL_DATABASE = [
+    // EGFR-mutant NSCLC Trials
+    {
+        nctId: 'NCT04816214',
+        title: 'Amivantamab + Lazertinib vs Osimertinib in EGFR-Mutant NSCLC (MARIPOSA)',
+        phase: 'Phase 3',
+        status: 'Active, not recruiting',
+        trialType: 'Interventional',
+        sponsor: 'Janssen',
+        conditions: ['NSCLC', 'EGFR-mutant'],
+        interventions: [
+            { type: 'Combination', name: 'Amivantamab + Lazertinib', mechanism: 'EGFR-MET bispecific + EGFR TKI', novelty: 'Combination' }
+        ],
+        eligibilityCriteria: {
+            ageRange: { min: 18, max: 99 },
+            gender: 'All',
+            performanceStatus: { scale: 'ECOG', maxValue: 1 },
+            priorTherapyRequirements: [
+                { requirement: 'Excluded', therapyType: 'Prior EGFR TKI', details: 'No prior EGFR TKI for metastatic disease' }
+            ],
+            organFunctionRequirements: [
+                { organ: 'Renal', parameter: 'CrCl', requirement: '≥50 mL/min' },
+                { organ: 'Hepatic', parameter: 'AST/ALT', requirement: '≤3x ULN' }
+            ],
+            exclusionCriteria: ['Active brain metastases', 'Prior EGFR TKI', 'Interstitial lung disease'],
+            inclusionCriteria: ['EGFR exon 19 del or L858R', 'Metastatic NSCLC', 'Treatment-naive']
+        },
+        locations: [
+            { facility: 'MD Anderson Cancer Center', city: 'Houston', state: 'TX', country: 'USA', status: 'Recruiting' },
+            { facility: 'Memorial Sloan Kettering', city: 'New York', state: 'NY', country: 'USA', status: 'Recruiting' }
+        ],
+        biomarkerRequirements: [
+            { biomarker: 'EGFR exon 19 del or L858R', requirement: 'Required', testMethod: ['NGS', 'PCR', 'ctDNA'] }
+        ],
+        primaryEndpoint: 'Progression-free survival',
+        estimatedEnrollment: 1074,
+        studyStartDate: '2021-05',
+        estimatedCompletionDate: '2025-12'
+    },
+    // HER2+ Breast Cancer Trials
+    {
+        nctId: 'NCT04784715',
+        title: 'Trastuzumab Deruxtecan vs Physician Choice in HER2-low Breast Cancer (DESTINY-Breast06)',
+        phase: 'Phase 3',
+        status: 'Recruiting',
+        trialType: 'Interventional',
+        sponsor: 'Daiichi Sankyo',
+        conditions: ['Breast Cancer', 'HER2-low'],
+        interventions: [
+            { type: 'Biological', name: 'Trastuzumab Deruxtecan', mechanism: 'HER2-directed ADC', novelty: 'New indication' }
+        ],
+        eligibilityCriteria: {
+            ageRange: { min: 18, max: 99 },
+            gender: 'All',
+            performanceStatus: { scale: 'ECOG', maxValue: 1 },
+            priorTherapyRequirements: [
+                { requirement: 'Required', therapyType: 'Prior endocrine therapy', details: 'For HR+ patients' },
+                { requirement: 'Allowed', therapyType: 'Prior chemotherapy', details: '1-2 prior lines allowed' }
+            ],
+            organFunctionRequirements: [
+                { organ: 'Cardiac', parameter: 'LVEF', requirement: '≥50%' }
+            ],
+            exclusionCriteria: ['HER2-positive (IHC 3+)', 'History of ILD', 'Uncontrolled brain mets'],
+            inclusionCriteria: ['HER2-low (IHC 1+ or 2+/FISH-)', 'HR+ or HR-', 'Metastatic breast cancer']
+        },
+        locations: [
+            { facility: 'Dana-Farber Cancer Institute', city: 'Boston', state: 'MA', country: 'USA', status: 'Recruiting' }
+        ],
+        biomarkerRequirements: [
+            { biomarker: 'HER2-low', requirement: 'Required', testMethod: ['IHC', 'FISH'] }
+        ],
+        primaryEndpoint: 'Progression-free survival',
+        estimatedEnrollment: 850,
+        studyStartDate: '2021-03',
+        estimatedCompletionDate: '2026-06'
+    },
+    // KRAS G12C Trials
+    {
+        nctId: 'NCT04685135',
+        title: 'Sotorasib + Anti-EGFR in KRAS G12C CRC (CodeBreaK 300)',
+        phase: 'Phase 3',
+        status: 'Recruiting',
+        trialType: 'Interventional',
+        sponsor: 'Amgen',
+        conditions: ['Colorectal Cancer', 'KRAS G12C'],
+        interventions: [
+            { type: 'Combination', name: 'Sotorasib + Panitumumab', mechanism: 'KRAS G12C inhibitor + anti-EGFR', novelty: 'Combination' }
+        ],
+        eligibilityCriteria: {
+            ageRange: { min: 18, max: 99 },
+            gender: 'All',
+            performanceStatus: { scale: 'ECOG', maxValue: 1 },
+            priorTherapyRequirements: [
+                { requirement: 'Required', therapyType: 'Prior chemotherapy', details: '1-2 prior lines for metastatic disease' }
+            ],
+            organFunctionRequirements: [],
+            exclusionCriteria: ['Prior KRAS G12C inhibitor', 'Symptomatic brain mets'],
+            inclusionCriteria: ['KRAS G12C mutation', 'Metastatic CRC', 'Prior fluoropyrimidine, oxaliplatin, irinotecan']
+        },
+        locations: [
+            { facility: 'Multiple sites', city: 'Various', state: 'Various', country: 'USA', status: 'Recruiting' }
+        ],
+        biomarkerRequirements: [
+            { biomarker: 'KRAS G12C', requirement: 'Required', testMethod: ['NGS', 'PCR'] }
+        ],
+        primaryEndpoint: 'Overall survival',
+        estimatedEnrollment: 160,
+        studyStartDate: '2021-01',
+        estimatedCompletionDate: '2025-06'
+    },
+    // Basket Trial Example
+    {
+        nctId: 'NCT02465060',
+        title: 'NCI-MATCH: Targeted Therapy Directed by Genetic Testing (Basket Trial)',
+        phase: 'Phase 2',
+        status: 'Active, not recruiting',
+        trialType: 'Basket',
+        sponsor: 'NCI',
+        conditions: ['Solid Tumors', 'Lymphoma'],
+        interventions: [
+            { type: 'Drug', name: 'Multiple targeted agents', mechanism: 'Various - based on molecular alteration', novelty: 'First-in-class' }
+        ],
+        eligibilityCriteria: {
+            ageRange: { min: 18, max: 99 },
+            gender: 'All',
+            performanceStatus: { scale: 'ECOG', maxValue: 1 },
+            priorTherapyRequirements: [
+                { requirement: 'Required', therapyType: 'Prior standard therapy', details: 'Progressed on standard options' }
+            ],
+            organFunctionRequirements: [],
+            exclusionCriteria: ['Matched targeted therapy previously received'],
+            inclusionCriteria: ['Actionable genomic alteration', 'No standard treatment options']
+        },
+        locations: [
+            { facility: 'ECOG-ACRIN Network Sites', city: 'Multiple', state: 'Multiple', country: 'USA', status: 'Recruiting' }
+        ],
+        biomarkerRequirements: [
+            { biomarker: 'Actionable mutation per NCI-MATCH arms', requirement: 'Required', testMethod: ['NGS'] }
+        ],
+        primaryEndpoint: 'Overall response rate',
+        estimatedEnrollment: 6000,
+        studyStartDate: '2015-08',
+        estimatedCompletionDate: '2025-12'
+    },
+    // Immunotherapy Combination
+    {
+        nctId: 'NCT03899610',
+        title: 'Nivolumab + Relatlimab vs Nivolumab in Melanoma (RELATIVITY-047)',
+        phase: 'Phase 3',
+        status: 'Active, not recruiting',
+        trialType: 'Interventional',
+        sponsor: 'Bristol-Myers Squibb',
+        conditions: ['Melanoma'],
+        interventions: [
+            { type: 'Combination', name: 'Nivolumab + Relatlimab', mechanism: 'Anti-PD-1 + Anti-LAG-3', novelty: 'First-in-class' }
+        ],
+        eligibilityCriteria: {
+            ageRange: { min: 18, max: 99 },
+            gender: 'All',
+            performanceStatus: { scale: 'ECOG', maxValue: 1 },
+            priorTherapyRequirements: [
+                { requirement: 'Excluded', therapyType: 'Prior anti-PD-1/PD-L1', details: 'No prior checkpoint inhibitor' }
+            ],
+            organFunctionRequirements: [],
+            exclusionCriteria: ['Active autoimmune disease', 'Prior immunotherapy'],
+            inclusionCriteria: ['Unresectable or metastatic melanoma', 'Treatment-naive for metastatic disease']
+        },
+        locations: [
+            { facility: 'Multiple sites', city: 'Various', state: 'Various', country: 'USA', status: 'Recruiting' }
+        ],
+        biomarkerRequirements: [],
+        primaryEndpoint: 'Progression-free survival',
+        estimatedEnrollment: 714,
+        studyStartDate: '2019-04',
+        estimatedCompletionDate: '2024-12'
+    },
+    // CAR-T Trial
+    {
+        nctId: 'NCT04503278',
+        title: 'Cilta-cel vs Standard of Care in Multiple Myeloma (CARTITUDE-4)',
+        phase: 'Phase 3',
+        status: 'Active, not recruiting',
+        trialType: 'Interventional',
+        sponsor: 'Janssen',
+        conditions: ['Multiple Myeloma'],
+        interventions: [
+            { type: 'Biological', name: 'Ciltacabtagene autoleucel (Cilta-cel)', mechanism: 'BCMA-directed CAR-T', novelty: 'Next-generation' }
+        ],
+        eligibilityCriteria: {
+            ageRange: { min: 18, max: 99 },
+            gender: 'All',
+            performanceStatus: { scale: 'ECOG', maxValue: 1 },
+            priorTherapyRequirements: [
+                { requirement: 'Required', therapyType: 'Prior lenalidomide and PI', details: '1-3 prior lines including lenalidomide and a PI' }
+            ],
+            organFunctionRequirements: [
+                { organ: 'Cardiac', parameter: 'LVEF', requirement: '≥45%' },
+                { organ: 'Pulmonary', parameter: 'O2 sat', requirement: '≥92% on room air' }
+            ],
+            exclusionCriteria: ['Prior BCMA-targeted therapy', 'Active CNS involvement', 'Uncontrolled infection'],
+            inclusionCriteria: ['Relapsed/refractory MM', 'Lenalidomide-refractory', '1-3 prior lines']
+        },
+        locations: [
+            { facility: 'Multiple academic centers', city: 'Various', state: 'Various', country: 'USA', status: 'Recruiting' }
+        ],
+        biomarkerRequirements: [],
+        primaryEndpoint: 'Progression-free survival',
+        estimatedEnrollment: 400,
+        studyStartDate: '2020-06',
+        estimatedCompletionDate: '2026-01'
+    },
+    // Pediatric Trial
+    {
+        nctId: 'NCT03155620',
+        title: 'Larotrectinib in Pediatric Solid Tumors with NTRK Fusion (SCOUT)',
+        phase: 'Phase 1/2',
+        status: 'Recruiting',
+        trialType: 'Basket',
+        sponsor: 'Bayer',
+        conditions: ['Pediatric Solid Tumors', 'NTRK Fusion'],
+        interventions: [
+            { type: 'Drug', name: 'Larotrectinib', mechanism: 'TRK inhibitor', novelty: 'First-in-class' }
+        ],
+        eligibilityCriteria: {
+            ageRange: { min: 0, max: 21 },
+            gender: 'All',
+            performanceStatus: { scale: 'Karnofsky', maxValue: 50 },
+            priorTherapyRequirements: [
+                { requirement: 'Allowed', therapyType: 'Prior therapy', details: 'No limit on prior therapies' }
+            ],
+            organFunctionRequirements: [],
+            exclusionCriteria: ['Prior TRK inhibitor', 'Primary CNS tumor'],
+            inclusionCriteria: ['NTRK gene fusion', 'Relapsed or refractory solid tumor', 'Age ≤21']
+        },
+        locations: [
+            { facility: "Children's Hospital of Philadelphia", city: 'Philadelphia', state: 'PA', country: 'USA', status: 'Recruiting' },
+            { facility: 'Texas Childrens Hospital', city: 'Houston', state: 'TX', country: 'USA', status: 'Recruiting' }
+        ],
+        biomarkerRequirements: [
+            { biomarker: 'NTRK1/2/3 fusion', requirement: 'Required', testMethod: ['NGS', 'FISH', 'IHC'] }
+        ],
+        primaryEndpoint: 'Overall response rate',
+        estimatedEnrollment: 150,
+        studyStartDate: '2017-07',
+        estimatedCompletionDate: '2025-12'
+    }
+];
+// ═══════════════════════════════════════════════════════════════════════════════
+// TRIAL MATCHING ENGINE
+// ═══════════════════════════════════════════════════════════════════════════════
+export class ClinicalTrialMatchingEngine {
+    trials = TRIAL_DATABASE;
+    findMatchingTrials(patient) {
+        const matches = [];
+        for (const trial of this.trials) {
+            if (trial.status === 'Withdrawn' || trial.status === 'Terminated')
+                continue;
+            const matchResult = this.evaluateTrialMatch(patient, trial);
+            if (matchResult.matchScore > 0) {
+                matches.push(matchResult);
+            }
+        }
+        return matches.sort((a, b) => b.matchScore - a.matchScore);
+    }
+    evaluateTrialMatch(patient, trial) {
+        const matchDetails = [];
+        const barriers = [];
+        let score = 0;
+        // Check cancer type match
+        const cancerMatch = trial.conditions.some(c => c.toLowerCase().includes(patient.cancerType.toLowerCase()) ||
+            patient.cancerType.toLowerCase().includes(c.toLowerCase()));
+        if (cancerMatch) {
+            score += 30;
+            matchDetails.push({ criterion: 'Cancer type', status: 'Met', explanation: 'Cancer type matches trial conditions' });
+        }
+        else {
+            matchDetails.push({ criterion: 'Cancer type', status: 'Not Met', explanation: 'Cancer type does not match' });
+        }
+        // Check biomarker requirements
+        for (const bioReq of trial.biomarkerRequirements) {
+            const patientBiomarker = patient.biomarkers.find(b => b.name.toLowerCase().includes(bioReq.biomarker.toLowerCase()) ||
+                bioReq.biomarker.toLowerCase().includes(b.name.toLowerCase()));
+            if (bioReq.requirement === 'Required') {
+                if (patientBiomarker?.status === 'Positive') {
+                    score += 25;
+                    matchDetails.push({ criterion: `Biomarker: ${bioReq.biomarker}`, status: 'Met', explanation: 'Required biomarker is positive' });
+                }
+                else if (patientBiomarker?.status === 'Negative') {
+                    score -= 50;
+                    barriers.push(`Required biomarker ${bioReq.biomarker} is negative`);
+                    matchDetails.push({ criterion: `Biomarker: ${bioReq.biomarker}`, status: 'Not Met', explanation: 'Required biomarker is negative' });
+                }
+                else {
+                    matchDetails.push({ criterion: `Biomarker: ${bioReq.biomarker}`, status: 'Unknown', explanation: 'Biomarker status not tested' });
+                }
+            }
+            else if (bioReq.requirement === 'Excluded') {
+                if (patientBiomarker?.status === 'Positive') {
+                    score -= 50;
+                    barriers.push(`Excluded biomarker ${bioReq.biomarker} is positive`);
+                    matchDetails.push({ criterion: `Biomarker: ${bioReq.biomarker}`, status: 'Not Met', explanation: 'Excluded biomarker is positive' });
+                }
+            }
+        }
+        // Check age eligibility
+        const ageElig = trial.eligibilityCriteria.ageRange;
+        if (patient.age >= ageElig.min && patient.age <= ageElig.max) {
+            score += 10;
+            matchDetails.push({ criterion: 'Age', status: 'Met', explanation: `Age ${patient.age} within range ${ageElig.min}-${ageElig.max}` });
+        }
+        else {
+            barriers.push(`Age ${patient.age} outside eligible range ${ageElig.min}-${ageElig.max}`);
+            matchDetails.push({ criterion: 'Age', status: 'Not Met', explanation: 'Age outside eligible range' });
+        }
+        // Check performance status
+        const psReq = trial.eligibilityCriteria.performanceStatus;
+        if (patient.performanceStatus <= psReq.maxValue) {
+            score += 10;
+            matchDetails.push({ criterion: 'Performance status', status: 'Met', explanation: `PS ${patient.performanceStatus} meets requirement ≤${psReq.maxValue}` });
+        }
+        else {
+            barriers.push(`Performance status ${patient.performanceStatus} exceeds maximum ${psReq.maxValue}`);
+            matchDetails.push({ criterion: 'Performance status', status: 'Not Met', explanation: 'Performance status too high' });
+        }
+        // Check phase preference
+        if (patient.preferences.preferredPhases.includes(trial.phase)) {
+            score += 5;
+        }
+        // Check location
+        const matchingLocation = trial.locations.find(loc => loc.country === patient.location.country &&
+            loc.status === 'Recruiting');
+        if (matchingLocation) {
+            score += 10;
+            matchDetails.push({ criterion: 'Location', status: 'Met', explanation: `Trial available in ${matchingLocation.city}, ${matchingLocation.state}` });
+        }
+        else if (patient.willingToTravel) {
+            score += 5;
+            matchDetails.push({ criterion: 'Location', status: 'Partial', explanation: 'Patient willing to travel' });
+        }
+        else {
+            barriers.push('No recruiting sites in patient location');
+            matchDetails.push({ criterion: 'Location', status: 'Not Met', explanation: 'No local sites; travel required' });
+        }
+        // Determine eligibility status
+        let eligibilityStatus;
+        if (barriers.length === 0 && score > 50) {
+            eligibilityStatus = 'Likely Eligible';
+        }
+        else if (barriers.length === 0) {
+            eligibilityStatus = 'Need More Info';
+        }
+        else if (barriers.some(b => b.includes('Required biomarker') || b.includes('Age'))) {
+            eligibilityStatus = 'Likely Ineligible';
+        }
+        else {
+            eligibilityStatus = 'Possibly Eligible';
+        }
+        // Generate next steps
+        const nextSteps = [];
+        if (eligibilityStatus === 'Likely Eligible' || eligibilityStatus === 'Possibly Eligible') {
+            nextSteps.push('Discuss with oncologist');
+            nextSteps.push(`Contact trial site: ${trial.locations[0]?.facility || 'See ClinicalTrials.gov'}`);
+            nextSteps.push(`Search ClinicalTrials.gov for NCT: ${trial.nctId}`);
+        }
+        if (matchDetails.some(m => m.status === 'Unknown')) {
+            nextSteps.push('Complete biomarker testing');
+        }
+        return {
+            trial,
+            matchScore: Math.max(0, score),
+            matchDetails,
+            eligibilityStatus,
+            barriers,
+            nextSteps
+        };
+    }
+    findTrialsByBiomarker(biomarker) {
+        return this.trials.filter(trial => trial.biomarkerRequirements.some(b => b.biomarker.toLowerCase().includes(biomarker.toLowerCase())));
+    }
+    findTrialsByMechanism(mechanism) {
+        return this.trials.filter(trial => trial.interventions.some(i => i.mechanism.toLowerCase().includes(mechanism.toLowerCase())));
+    }
+    findBasketTrials() {
+        return this.trials.filter(trial => trial.trialType === 'Basket');
+    }
+    findPediatricTrials() {
+        return this.trials.filter(trial => trial.eligibilityCriteria.ageRange.min < 18 ||
+            trial.conditions.some(c => c.toLowerCase().includes('pediatric')));
+    }
+    getTrialById(nctId) {
+        return this.trials.find(t => t.nctId === nctId);
+    }
+    generateTrialSearchStrategy(patient) {
+        const searchTerms = [
+            patient.cancerType,
+            patient.histology,
+            ...patient.biomarkers.filter(b => b.status === 'Positive').map(b => b.name)
+        ];
+        return {
+            searchTerms,
+            recommendedDatabases: [
+                'ClinicalTrials.gov (clinicaltrials.gov)',
+                'NCI Cancer Clinical Trials (cancer.gov/clinicaltrials)',
+                'TrialMatch (lls.org/support/information-specialists)',
+                'EmergingMed Navigator (emergingmed.com)'
+            ],
+            searchTips: [
+                'Use condition + biomarker for targeted searches',
+                'Filter by "Recruiting" status',
+                'Check Phase 1/2 trials for novel mechanisms',
+                'Consider basket trials if you have an actionable mutation',
+                'Contact trial coordinators directly for eligibility questions'
+            ]
+        };
+    }
+}
+// Export singleton
+export const clinicalTrialMatchingEngine = new ClinicalTrialMatchingEngine();
+//# sourceMappingURL=clinicalTrialMatchingModule.js.map

package/dist/capabilities/clinicalTrialMatchingModule.js.map

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package/dist/capabilities/cureValidationFramework.d.ts

@@ -0,0 +1,195 @@
+/**
+ * 癌症治愈验证框架 (Cancer Cure Validation Framework)
+ *
+ * ██╗   ██╗ █████╗ ██╗     ██╗██████╗  █████╗ ████████╗███████╗
+ * ██║   ██║██╔══██╗██║     ██║██╔══██╗██╔══██╗╚══██╔══╝██╔════╝
+ * ██║   ██║███████║██║     ██║██║  ██║███████║   ██║   █████╗
+ * ╚██╗ ██╔╝██╔══██║██║     ██║██║  ██║██╔══██║   ██║   ██╔══╝
+ *  ╚████╔╝ ██║  ██║███████╗██║██████╔╝██║  ██║   ██║   ███████╗
+ *   ╚═══╝  ╚═╝  ╚═╝╚══════╝╚═╝╚═════╝ ╚═╝  ╚═╝   ╚═╝   ╚══════╝
+ *
+ * Comprehensive validation ensuring:
+ * - 完整性验证 (Coverage Completeness)
+ * - 治疗效果验证 (Treatment Efficacy Validation)
+ * - 生存率监测 (Survival Monitoring)
+ * - 治愈认证 (Cure Certification)
+ * - 复发监测 (Recurrence Surveillance)
+ */
+export interface CancerCoverageValidation {
+    cancerType: string;
+    icd10Code: string;
+    icdoMorphology: string;
+    hasTreatmentProtocol: boolean;
+    hasGlobalGuidelines: boolean;
+    hasResourceLimitedAdaptation: boolean;
+    hasPediatricProtocol: boolean;
+    hasEmergingTherapy: boolean;
+    hasSupportiveCare: boolean;
+    coverageScore: number;
+    gaps: string[];
+    recommendations: string[];
+}
+export interface TreatmentOutcomeValidation {
+    patientId: string;
+    cancerType: string;
+    stage: string;
+    treatmentProtocol: string;
+    startDate: Date;
+    currentStatus: 'active_treatment' | 'response' | 'stable' | 'progression' | 'remission' | 'cure_pending' | 'cured';
+    responseAssessment: {
+        method: 'RECIST' | 'iRECIST' | 'RANO' | 'Lugano' | 'IMWG' | 'Other';
+        result: 'CR' | 'PR' | 'SD' | 'PD' | 'NE';
+        date: Date;
+    };
+    biomarkerResponse?: {
+        marker: string;
+        baseline: number;
+        current: number;
+        percentChange: number;
+    }[];
+    molecularResponse?: {
+        mrdStatus: 'positive' | 'negative' | 'not_assessed';
+        ctdnaStatus?: 'detected' | 'not_detected' | 'not_assessed';
+        sensitivity: string;
+    };
+    nextAssessment: Date;
+}
+export interface CureCriteria {
+    cancerType: string;
+    definition: string;
+    timeRequirement: string;
+    biomarkerRequirements: string[];
+    imagingRequirements: string[];
+    clinicalRequirements: string[];
+    surveillanceProtocol: string[];
+    lateEffectsMonitoring: string[];
+}
+export interface CureVerification {
+    patientId: string;
+    cancerType: string;
+    diagnosisDate: Date;
+    treatmentCompletionDate: Date;
+    currentDate: Date;
+    timeSinceCompletion: string;
+    cureStatus: 'pending' | 'conditional' | 'verified' | 'not_applicable';
+    criteriaMetStatus: {
+        criterion: string;
+        met: boolean;
+        evidence: string;
+    }[];
+    overallConfidence: number;
+    nextVerificationDate: Date;
+    surveillanceSchedule: {
+        assessment: string;
+        date: Date;
+    }[];
+}
+export interface ComprehensiveCoverageReport {
+    generatedAt: Date;
+    totalCancerTypes: number;
+    coveredCancerTypes: number;
+    coveragePercentage: number;
+    byCategory: {
+        solidTumors: {
+            total: number;
+            covered: number;
+        };
+        hematologic: {
+            total: number;
+            covered: number;
+        };
+        pediatric: {
+            total: number;
+            covered: number;
+        };
+        rare: {
+            total: number;
+            covered: number;
+        };
+    };
+    byRegion: {
+        nccn: number;
+        esmo: number;
+        asian: number;
+        african: number;
+        latinAmerican: number;
+        who: number;
+    };
+    gaps: CancerCoverageValidation[];
+    recommendations: string[];
+}
+export declare const COMPLETE_CANCER_TAXONOMY: {
+    solidTumors: {
+        headAndNeck: string[];
+        thoracic: string[];
+        breast: string[];
+        giUpper: string[];
+        giLower: string[];
+        hepatobiliary: string[];
+        pancreas: string[];
+        genitourinary: string[];
+        gynecologic: string[];
+        skin: string[];
+        cns: string[];
+        bone: string[];
+        softTissue: string[];
+        neuroendocrine: string[];
+        rare: string[];
+    };
+    hematologic: {
+        leukemia: string[];
+        lymphoma: string[];
+        plasmaCell: string[];
+        mpn: string[];
+        mds: string[];
+    };
+    pediatric: {
+        solid: string[];
+        cns: string[];
+        hematologic: string[];
+    };
+};
+export declare const CURE_CRITERIA_DATABASE: CureCriteria[];
+export declare class CureValidationFramework {
+    /**
+     * Validate comprehensive cancer coverage
+     */
+    validateCoverageCompleteness(): Promise<ComprehensiveCoverageReport>;
+    /**
+     * Verify patient cure status
+     */
+    verifyCureStatus(patientId: string, cancerType: string, treatmentHistory: TreatmentOutcomeValidation): Promise<CureVerification>;
+    /**
+     * Generate coverage validation for a specific cancer type
+     */
+    validateCancerCoverage(cancerType: string): Promise<CancerCoverageValidation>;
+    /**
+     * Get all cancer types from taxonomy
+     */
+    private getAllCancerTypes;
+    private assessCoveredTypes;
+    private calculateCategoryBreakdown;
+    private calculateRegionalBreakdown;
+    private generateCoverageRecommendations;
+    private calculateTimeSince;
+    private evaluateCriteria;
+    private calculateCureConfidence;
+    private determineCureStatus;
+    private calculateNextVerification;
+    private generateSurveillanceSchedule;
+    private generateGenericCureVerification;
+    private calculateCoverageScore;
+    private getICD10Code;
+    private getICDOMorphology;
+    /**
+     * Get coverage statistics summary
+     */
+    getCoverageStatistics(): {
+        totalCancerTypesInTaxonomy: number;
+        solidTumorCategories: number;
+        hematologicCategories: number;
+        pediatricCategories: number;
+        cureCriteriaDefined: number;
+    };
+}
+//# sourceMappingURL=cureValidationFramework.d.ts.map