/**
 * Comprehensive Treatment Sequencing and Line-of-Therapy Protocols
 *
 * ╔═══════════════════════════════════════════════════════════════════════════════╗
 * ║  TREATMENT SEQUENCING ENGINE - OPTIMAL THERAPY ORDERING FOR CURE             ║
 * ╠═══════════════════════════════════════════════════════════════════════════════╣
 * ║  This module provides:                                                        ║
 * ║  - Complete line-of-therapy protocols for all cancer types                   ║
 * ║  - Evidence-based treatment sequencing algorithms                            ║
 * ║  - Biomarker-guided therapy selection                                        ║
 * ║  - Combination vs sequential therapy decision support                        ║
 * ║  - Treatment switching criteria and timing                                   ║
 * ║  - Maintenance therapy protocols                                             ║
 * ║  - Rechallenge strategies after treatment holiday                            ║
 * ╚═══════════════════════════════════════════════════════════════════════════════╝
 */
export interface TreatmentLine {
    line: '1L' | '2L' | '3L' | '4L' | '5L+' | 'Maintenance' | 'Neoadjuvant' | 'Adjuvant' | 'Consolidation';
    setting: 'Curative' | 'Palliative' | 'Definitive' | 'Salvage';
    regimens: TherapyRegimen[];
    selectionCriteria: SelectionCriteria;
    responseAssessment: ResponseAssessment;
    switchingCriteria: SwitchingCriteria;
}
export interface TherapyRegimen {
    id: string;
    name: string;
    drugs: DrugComponent[];
    schedule: string;
    duration: string;
    evidenceLevel: 'Category 1' | 'Category 2A' | 'Category 2B' | 'Category 3';
    preferenceLevel: 'Preferred' | 'Other Recommended' | 'Useful in Certain Circumstances';
    keyTrials: string[];
    expectedOutcomes: {
        responseRate: string;
        pfs: string;
        os: string;
    };
    biomarkerRequirements?: BiomarkerRequirement[];
    contraindications: string[];
    specialConsiderations: string[];
}
export interface DrugComponent {
    name: string;
    class: string;
    dose: string;
    route: 'IV' | 'PO' | 'SC' | 'IM' | 'IT' | 'Topical';
    schedule: string;
    doseModifications?: DoseModification[];
}
export interface DoseModification {
    indication: string;
    adjustment: string;
}
export interface SelectionCriteria {
    biomarkers: BiomarkerRequirement[];
    performanceStatus: string;
    organFunction: string[];
    priorTherapies: string[];
    patientPreferences: string[];
}
export interface BiomarkerRequirement {
    marker: string;
    requirement: 'Required Positive' | 'Required Negative' | 'Preferred Positive' | 'Preferred Negative' | 'Predictive';
    testMethod: string[];
    threshold?: string;
}
export interface ResponseAssessment {
    method: string[];
    timing: string;
    criteria: 'RECIST 1.1' | 'iRECIST' | 'RANO' | 'Lugano' | 'PCWG3' | 'mRECIST' | 'Cheson';
    minimalResidualDisease?: boolean;
}
export interface SwitchingCriteria {
    progressionDefinition: string;
    toxicityCriteria: string;
    ctDNAGuidance?: string;
    imagingInterval: string;
    mandatorySwitch: string[];
    optionalSwitch: string[];
}
export interface CancerTreatmentSequence {
    cancerType: string;
    molecularSubtype?: string;
    stage: string;
    treatmentIntent: 'Curative' | 'Life-Prolonging' | 'Palliative';
    lines: TreatmentLine[];
    specialPathways: SpecialPathway[];
    maintenanceOptions: MaintenanceProtocol[];
    rechallengeOptions: RechallengeProtocol[];
}
export interface SpecialPathway {
    name: string;
    eligibility: string[];
    protocol: string;
    rationale: string;
}
export interface MaintenanceProtocol {
    name: string;
    eligibility: string[];
    regimen: TherapyRegimen;
    duration: string;
    monitoringSchedule: string;
}
export interface RechallengeProtocol {
    originalTherapy: string;
    eligibility: string[];
    washoutPeriod: string;
    expectedResponse: string;
    monitoringIntensity: string;
}
export declare const NSCLC_TREATMENT_SEQUENCES: CancerTreatmentSequence[];
export declare const BREAST_CANCER_TREATMENT_SEQUENCES: CancerTreatmentSequence[];
export declare const COLORECTAL_CANCER_TREATMENT_SEQUENCES: CancerTreatmentSequence[];
export declare class TreatmentSequencingEngine {
    private sequences;
    constructor();
    private initializeSequences;
    getSequence(cancerType: string, molecularSubtype?: string, stage?: string): CancerTreatmentSequence | undefined;
    getLineOfTherapy(cancerType: string, molecularSubtype: string | undefined, line: TreatmentLine['line']): TreatmentLine | undefined;
    getNextLineRecommendation(cancerType: string, molecularSubtype: string | undefined, currentLine: TreatmentLine['line'], priorRegimens: string[], biomarkerProfile: Record<string, string>): TherapyRegimen[];
    assessResponseAndRecommendSwitch(currentRegimen: TherapyRegimen, responseStatus: 'CR' | 'PR' | 'SD' | 'PD', toxicityGrade: number, cancerType: string, molecularSubtype?: string): {
        recommendation: 'continue' | 'switch' | 'maintain';
        reasoning: string;
        suggestedActions: string[];
    };
    getSpecialPathway(cancerType: string, molecularSubtype: string | undefined, biomarkerProfile: Record<string, string>): SpecialPathway | undefined;
    getRechallengeOptions(cancerType: string, molecularSubtype: string | undefined, priorTherapy: string): RechallengeProtocol | undefined;
    generateTreatmentRoadmap(cancerType: string, molecularSubtype: string | undefined, stage: string, biomarkerProfile: Record<string, string>): {
        lines: Array<{
            line: string;
            options: TherapyRegimen[];
            decisionPoints: string[];
        }>;
        specialConsiderations: string[];
        clinicalTrialOpportunities: string[];
    };
}
export declare const treatmentSequencingEngine: TreatmentSequencingEngine;
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