/**
 * Multimodal Oncology - Radiation and Surgical Oncology Integration
 *
 * ╔═══════════════════════════════════════════════════════════════════════════════╗
 * ║  MULTIMODAL ONCOLOGY - RADIATION AND SURGICAL TREATMENT INTEGRATION          ║
 * ╠═══════════════════════════════════════════════════════════════════════════════╣
 * ║  This module provides:                                                        ║
 * ║  - Radiation oncology protocols and dose calculations                        ║
 * ║  - Surgical oncology decision support                                        ║
 * ║  - Multimodal treatment sequencing                                           ║
 * ║  - Toxicity prediction and management                                        ║
 * ║  - Re-irradiation considerations                                             ║
 * ╚═══════════════════════════════════════════════════════════════════════════════╝
 */

// ═══════════════════════════════════════════════════════════════════════════════
// RADIATION ONCOLOGY DEFINITIONS
// ═══════════════════════════════════════════════════════════════════════════════

export interface RadiationProtocol {
  indication: string;
  intent: 'Curative' | 'Adjuvant' | 'Neoadjuvant' | 'Palliative' | 'Definitive';
  technique: RadiationTechnique;
  fractionation: FractionationScheme[];
  targetVolumes: TargetVolume[];
  organAtRiskConstraints: OARConstraint[];
  combinationTherapy?: ConcurrentTherapy;
  expectedOutcomes: RadiationOutcome;
  toxicityProfile: RadiationToxicity;
}

export interface RadiationTechnique {
  modality: 'Photon EBRT' | 'IMRT' | 'VMAT' | 'SBRT/SABR' | 'SRS' | 'Proton' | 'Carbon Ion' | 'Brachytherapy' | 'TBI';
  deliveryMethod: string;
  imagingGuidance: string[];
  motionManagement?: string;
}

export interface FractionationScheme {
  name: string;
  totalDose: number;
  fractions: number;
  dosePerFraction: number;
  schedule: string;
  indication: string;
  biologicalEquivalentDose?: number; // BED
}

export interface TargetVolume {
  name: 'GTV' | 'CTV' | 'PTV' | 'ITV';
  description: string;
  margin: string;
  dose: number;
}

export interface OARConstraint {
  organ: string;
  constraint: string;
  toxicityEndpoint: string;
  priority: 'Hard' | 'Soft';
}

export interface ConcurrentTherapy {
  agent: string;
  schedule: string;
  rationale: string;
  precautions: string[];
}

export interface RadiationOutcome {
  localControl: string;
  survivalBenefit: string;
  evidenceBasis: string;
}

export interface RadiationToxicity {
  acute: ToxicityEvent[];
  late: ToxicityEvent[];
  managementStrategies: string[];
}

export interface ToxicityEvent {
  type: string;
  incidence: string;
  severity: string;
  timing: string;
  management: string;
}

// ═══════════════════════════════════════════════════════════════════════════════
// RADIATION PROTOCOLS BY SITE
// ═══════════════════════════════════════════════════════════════════════════════

export const RADIATION_PROTOCOLS: Record<string, RadiationProtocol[]> = {
  'lung-nsclc-early': [
    {
      indication: 'Early-stage NSCLC (Stage I-II) - Medically Inoperable',
      intent: 'Curative',
      technique: {
        modality: 'SBRT/SABR',
        deliveryMethod: 'VMAT or 3D-CRT',
        imagingGuidance: ['CBCT', '4D-CT for motion assessment'],
        motionManagement: 'Abdominal compression, gating, or tracking'
      },
      fractionation: [
        {
          name: 'Standard SBRT',
          totalDose: 54,
          fractions: 3,
          dosePerFraction: 18,
          schedule: 'Every other day x 3',
          indication: 'Peripheral tumors',
          biologicalEquivalentDose: 151
        },
        {
          name: 'Central SBRT',
          totalDose: 50,
          fractions: 5,
          dosePerFraction: 10,
          schedule: 'Daily or every other day x 5',
          indication: 'Central tumors (within 2cm of bronchial tree)',
          biologicalEquivalentDose: 100
        },
        {
          name: 'Ultra-central',
          totalDose: 60,
          fractions: 8,
          dosePerFraction: 7.5,
          schedule: 'Every other day',
          indication: 'Ultra-central tumors',
          biologicalEquivalentDose: 105
        }
      ],
      targetVolumes: [
        { name: 'GTV', description: 'Gross tumor on imaging', margin: '0', dose: 54 },
        { name: 'ITV', description: 'Internal target volume (4D-CT)', margin: 'Motion envelope', dose: 54 },
        { name: 'PTV', description: 'Planning target volume', margin: '3-5mm from ITV', dose: 54 }
      ],
      organAtRiskConstraints: [
        { organ: 'Spinal cord', constraint: 'Dmax < 18 Gy (3 fx) or 30 Gy (5 fx)', toxicityEndpoint: 'Myelopathy', priority: 'Hard' },
        { organ: 'Esophagus', constraint: 'Dmax < 25 Gy (3 fx)', toxicityEndpoint: 'Esophagitis, stricture', priority: 'Hard' },
        { organ: 'Heart', constraint: 'Dmax < 30 Gy (3 fx)', toxicityEndpoint: 'Pericarditis', priority: 'Hard' },
        { organ: 'Brachial plexus', constraint: 'Dmax < 24 Gy (3 fx)', toxicityEndpoint: 'Plexopathy', priority: 'Hard' },
        { organ: 'Chest wall', constraint: 'V30 < 30cc', toxicityEndpoint: 'Rib fracture, pain', priority: 'Soft' }
      ],
      expectedOutcomes: {
        localControl: '90-95% at 3 years',
        survivalBenefit: '50-60% OS at 3 years for inoperable patients',
        evidenceBasis: 'RTOG 0236, RTOG 0618, Multiple institutional series'
      },
      toxicityProfile: {
        acute: [
          { type: 'Fatigue', incidence: '30-50%', severity: 'Mild-moderate', timing: 'During treatment', management: 'Supportive care' },
          { type: 'Cough', incidence: '20-30%', severity: 'Mild', timing: '1-2 weeks post-treatment', management: 'Antitussives' }
        ],
        late: [
          { type: 'Radiation pneumonitis', incidence: '10-15%', severity: 'Grade 2-3 in 5%', timing: '1-6 months', management: 'Steroids if symptomatic' },
          { type: 'Chest wall pain/rib fracture', incidence: '5-10%', severity: 'Mild-moderate', timing: '6-24 months', management: 'Analgesics' }
        ],
        managementStrategies: ['Baseline and follow-up PFTs', 'CT surveillance', 'Smoking cessation']
      }
    }
  ],
  'lung-nsclc-locally-advanced': [
    {
      indication: 'Locally Advanced NSCLC (Stage III) - Definitive Chemoradiation',
      intent: 'Definitive',
      technique: {
        modality: 'IMRT',
        deliveryMethod: 'VMAT preferred',
        imagingGuidance: ['Daily CBCT', '4D-CT planning'],
        motionManagement: 'ITV approach or gating'
      },
      fractionation: [
        {
          name: 'Standard fractionation',
          totalDose: 60,
          fractions: 30,
          dosePerFraction: 2,
          schedule: 'Daily, Monday-Friday',
          indication: 'Standard for concurrent chemoradiation',
          biologicalEquivalentDose: 72
        }
      ],
      targetVolumes: [
        { name: 'GTV', description: 'Primary tumor + involved nodes', margin: '0', dose: 60 },
        { name: 'CTV', description: 'GTV + microscopic extension', margin: '5-8mm (anatomically constrained)', dose: 60 },
        { name: 'PTV', description: 'CTV + setup uncertainty', margin: '5mm', dose: 60 }
      ],
      organAtRiskConstraints: [
        { organ: 'Lung (bilateral)', constraint: 'V20 < 35%, Mean lung dose < 20 Gy', toxicityEndpoint: 'Pneumonitis', priority: 'Soft' },
        { organ: 'Spinal cord', constraint: 'Dmax < 45 Gy', toxicityEndpoint: 'Myelopathy', priority: 'Hard' },
        { organ: 'Esophagus', constraint: 'Mean < 34 Gy, V60 < 17%', toxicityEndpoint: 'Esophagitis', priority: 'Soft' },
        { organ: 'Heart', constraint: 'Mean < 26 Gy, V50 < 25%', toxicityEndpoint: 'Cardiac toxicity', priority: 'Soft' }
      ],
      combinationTherapy: {
        agent: 'Platinum-doublet (cisplatin/etoposide or carboplatin/paclitaxel)',
        schedule: 'Weekly or every 3 weeks during radiation',
        rationale: 'Radiosensitization, improved survival',
        precautions: ['Monitor counts', 'Nephrotoxicity with cisplatin', 'Esophagitis may be worse']
      },
      expectedOutcomes: {
        localControl: '60-70% at 2 years',
        survivalBenefit: 'Median OS 28-29 months with durvalumab consolidation',
        evidenceBasis: 'RTOG 0617, PACIFIC trial'
      },
      toxicityProfile: {
        acute: [
          { type: 'Esophagitis', incidence: '60-80%', severity: 'Grade 3 in 15-20%', timing: 'Weeks 3-6', management: 'Lidocaine viscous, PPI, soft diet' },
          { type: 'Fatigue', incidence: '80%', severity: 'Moderate', timing: 'Throughout', management: 'Rest, activity as tolerated' },
          { type: 'Myelosuppression', incidence: '50-70%', severity: 'Variable', timing: 'Throughout', management: 'Hold chemo if needed, G-CSF' }
        ],
        late: [
          { type: 'Radiation pneumonitis', incidence: '15-30%', severity: 'Grade 3 in 5-10%', timing: '1-6 months', management: 'Steroids' },
          { type: 'Cardiac events', incidence: '5-10%', severity: 'Variable', timing: 'Years', management: 'Cardiology follow-up' }
        ],
        managementStrategies: ['Weekly on-treatment visits', 'Nutritional support', 'PFT monitoring']
      }
    }
  ],
  'breast-adjuvant': [
    {
      indication: 'Breast Cancer - Adjuvant Whole Breast Radiation after Lumpectomy',
      intent: 'Adjuvant',
      technique: {
        modality: 'IMRT',
        deliveryMethod: 'Tangential fields or VMAT',
        imagingGuidance: ['Surface guidance (AlignRT)', 'CBCT weekly'],
        motionManagement: 'Deep inspiration breath hold (DIBH) for left-sided'
      },
      fractionation: [
        {
          name: 'Conventional fractionation',
          totalDose: 50,
          fractions: 25,
          dosePerFraction: 2,
          schedule: 'Daily, Monday-Friday',
          indication: 'Standard approach',
          biologicalEquivalentDose: 60
        },
        {
          name: 'Hypofractionation',
          totalDose: 40,
          fractions: 15,
          dosePerFraction: 2.67,
          schedule: 'Daily, Monday-Friday',
          indication: 'Preferred for most patients',
          biologicalEquivalentDose: 58
        },
        {
          name: 'Ultra-hypofractionation',
          totalDose: 26,
          fractions: 5,
          dosePerFraction: 5.2,
          schedule: 'Weekly x 5',
          indication: 'Select patients, FAST-Forward regimen',
          biologicalEquivalentDose: 54
        }
      ],
      targetVolumes: [
        { name: 'CTV', description: 'Whole breast (chest wall if mastectomy)', margin: 'Anatomic', dose: 40 },
        { name: 'PTV', description: 'CTV + setup margin', margin: '5mm (skin flash)', dose: 40 }
      ],
      organAtRiskConstraints: [
        { organ: 'Heart (left-sided)', constraint: 'Mean < 4 Gy, V25 < 10%', toxicityEndpoint: 'Coronary disease', priority: 'Soft' },
        { organ: 'Lung (ipsilateral)', constraint: 'V20 < 30%', toxicityEndpoint: 'Pneumonitis', priority: 'Soft' },
        { organ: 'Contralateral breast', constraint: 'Mean < 3 Gy', toxicityEndpoint: 'Second malignancy', priority: 'Soft' }
      ],
      expectedOutcomes: {
        localControl: 'Reduces local recurrence by 50%',
        survivalBenefit: '5-10% improvement in breast cancer-specific survival at 15 years',
        evidenceBasis: 'EBCTCG meta-analysis, START trials, FAST-Forward'
      },
      toxicityProfile: {
        acute: [
          { type: 'Skin reaction (erythema, desquamation)', incidence: '90%', severity: 'Grade 2-3 in 30%', timing: 'Weeks 3-6', management: 'Aquaphor, Silvadene if moist' },
          { type: 'Fatigue', incidence: '60%', severity: 'Mild-moderate', timing: 'Throughout', management: 'Rest' }
        ],
        late: [
          { type: 'Breast fibrosis/cosmetic change', incidence: '10-20%', severity: 'Mild in most', timing: 'Months-years', management: 'Pentoxifylline/vitamin E' },
          { type: 'Lymphedema', incidence: '5-10% (higher with nodal RT)', severity: 'Variable', timing: 'Months-years', management: 'Physical therapy, compression' }
        ],
        managementStrategies: ['Weekly skin assessment', 'Arm exercise program', 'DIBH for left-sided']
      }
    }
  ],
  'prostate-definitive': [
    {
      indication: 'Prostate Cancer - Definitive Radiation',
      intent: 'Curative',
      technique: {
        modality: 'IMRT',
        deliveryMethod: 'VMAT',
        imagingGuidance: ['Daily CBCT or fiducial tracking', 'MRI fusion for planning'],
        motionManagement: 'Rectal spacer (SpaceOAR) recommended'
      },
      fractionation: [
        {
          name: 'Conventional',
          totalDose: 78,
          fractions: 39,
          dosePerFraction: 2,
          schedule: 'Daily, Monday-Friday',
          indication: 'Standard for higher-risk disease',
          biologicalEquivalentDose: 137
        },
        {
          name: 'Moderate hypofractionation',
          totalDose: 70,
          fractions: 28,
          dosePerFraction: 2.5,
          schedule: 'Daily, Monday-Friday',
          indication: 'Non-inferior to conventional',
          biologicalEquivalentDose: 141
        },
        {
          name: 'Ultra-hypofractionation/SBRT',
          totalDose: 36.25,
          fractions: 5,
          dosePerFraction: 7.25,
          schedule: 'Every other day',
          indication: 'Low to intermediate risk',
          biologicalEquivalentDose: 158
        }
      ],
      targetVolumes: [
        { name: 'CTV', description: 'Prostate ± seminal vesicles', margin: 'Anatomic', dose: 78 },
        { name: 'PTV', description: 'CTV + setup margin', margin: '3-5mm (smaller posteriorly)', dose: 78 }
      ],
      organAtRiskConstraints: [
        { organ: 'Rectum', constraint: 'V70 < 15%, V50 < 50%', toxicityEndpoint: 'Rectal toxicity', priority: 'Soft' },
        { organ: 'Bladder', constraint: 'V70 < 25%, V65 < 50%', toxicityEndpoint: 'Cystitis', priority: 'Soft' },
        { organ: 'Femoral heads', constraint: 'V50 < 5%', toxicityEndpoint: 'Avascular necrosis', priority: 'Soft' }
      ],
      combinationTherapy: {
        agent: 'ADT (GnRH agonist ± antiandrogen)',
        schedule: 'Intermediate risk: 4-6 months; High risk: 18-36 months',
        rationale: 'Improved survival with ADT in intermediate and high risk',
        precautions: ['Cardiovascular risk', 'Bone health', 'Metabolic effects']
      },
      expectedOutcomes: {
        localControl: '90-95% biochemical control at 5 years for intermediate risk',
        survivalBenefit: 'Equivalent to surgery; 10-year CSS >90% for intermediate risk',
        evidenceBasis: 'ProtecT, PROFIT, CHHiP, PACE trials'
      },
      toxicityProfile: {
        acute: [
          { type: 'Urinary frequency/urgency', incidence: '40-60%', severity: 'Mild-moderate', timing: 'During and weeks after', management: 'Alpha-blockers, anticholinergics' },
          { type: 'Bowel symptoms (diarrhea, urgency)', incidence: '30-40%', severity: 'Mild-moderate', timing: 'During and weeks after', management: 'Loperamide, low-residue diet' }
        ],
        late: [
          { type: 'Erectile dysfunction', incidence: '30-50%', severity: 'Variable', timing: 'Months-years', management: 'PDE5 inhibitors, penile rehabilitation' },
          { type: 'Rectal bleeding', incidence: '5-10%', severity: 'Usually mild', timing: 'Months-years', management: 'Observation, argon plasma coagulation if severe' }
        ],
        managementStrategies: ['SpaceOAR hydrogel', 'Daily image guidance', 'Bladder/rectal filling protocols']
      }
    }
  ],
  'palliative-bone': [
    {
      indication: 'Painful Bone Metastases - Palliative',
      intent: 'Palliative',
      technique: {
        modality: 'Photon EBRT',
        deliveryMethod: '3D-CRT or simple fields',
        imagingGuidance: ['Portal imaging or kV'],
        motionManagement: 'None typically required'
      },
      fractionation: [
        {
          name: 'Single fraction',
          totalDose: 8,
          fractions: 1,
          dosePerFraction: 8,
          schedule: 'Single treatment',
          indication: 'Preferred for most uncomplicated bone mets',
          biologicalEquivalentDose: 14
        },
        {
          name: 'Short course',
          totalDose: 20,
          fractions: 5,
          dosePerFraction: 4,
          schedule: 'Daily x 5',
          indication: 'Alternative to single fraction',
          biologicalEquivalentDose: 27
        },
        {
          name: 'Longer course',
          totalDose: 30,
          fractions: 10,
          dosePerFraction: 3,
          schedule: 'Daily x 10',
          indication: 'Larger treatment volumes, spinal cord compression',
          biologicalEquivalentDose: 39
        }
      ],
      targetVolumes: [
        { name: 'GTV', description: 'Visible metastasis', margin: '0', dose: 8 },
        { name: 'CTV', description: 'GTV + margin for subclinical disease', margin: '1 vertebral body above/below for spine', dose: 8 },
        { name: 'PTV', description: 'CTV + setup margin', margin: '0.5-1cm', dose: 8 }
      ],
      organAtRiskConstraints: [
        { organ: 'Spinal cord', constraint: 'Dmax varies by fractionation', toxicityEndpoint: 'Myelopathy', priority: 'Hard' }
      ],
      expectedOutcomes: {
        localControl: '70-80% pain response',
        survivalBenefit: 'N/A - palliative intent',
        evidenceBasis: 'RTOG 9714, Dutch Bone Metastasis Study'
      },
      toxicityProfile: {
        acute: [
          { type: 'Pain flare', incidence: '30-40%', severity: 'Mild-moderate', timing: '24-48h post-treatment', management: 'Dexamethasone premedication reduces' },
          { type: 'Nausea (abdominal sites)', incidence: '20-30%', severity: 'Mild', timing: 'During/after', management: 'Antiemetics' }
        ],
        late: [
          { type: 'Pathologic fracture risk', incidence: 'Varies', severity: 'N/A', timing: 'Any time', management: 'Orthopedic evaluation for impending fracture' }
        ],
        managementStrategies: ['Pain reassessment at 4 weeks', 'Consider retreatment if incomplete response', 'Bisphosphonates/denosumab']
      }
    }
  ]
};

// ═══════════════════════════════════════════════════════════════════════════════
// SURGICAL ONCOLOGY DEFINITIONS
// ═══════════════════════════════════════════════════════════════════════════════

export interface SurgicalProcedure {
  name: string;
  indication: string;
  intent: 'Curative' | 'Debulking' | 'Palliative' | 'Diagnostic' | 'Prophylactic';
  approach: SurgicalApproach[];
  oncologicPrinciples: string[];
  margins: MarginRequirement;
  lymphNodeAssessment: LymphNodeProtocol;
  perioperativeConsiderations: PerioperativeProtocol;
  outcomes: SurgicalOutcome;
}

export interface SurgicalApproach {
  technique: 'Open' | 'Laparoscopic' | 'Robotic' | 'Endoscopic' | 'Percutaneous';
  advantages: string[];
  disadvantages: string[];
  patientSelection: string[];
}

export interface MarginRequirement {
  recommended: string;
  minimum: string;
  impactOfPositiveMargin: string;
}

export interface LymphNodeProtocol {
  type: 'Sentinel Node' | 'Regional Dissection' | 'Sampling' | 'None';
  minimumNodes?: number;
  technique: string;
  indication: string;
}

export interface PerioperativeProtocol {
  preoperativeOptimization: string[];
  erpsProtocol: boolean;
  vteProhylaxis: string;
  antibioticProphylaxis: string;
  nutritionalConsiderations: string;
  neoadjuvantOptions?: string;
  adjuvantOptions?: string;
}

export interface SurgicalOutcome {
  mortality: string;
  morbidity: string;
  hospitalStay: string;
  oncologicOutcome: string;
}

// ═══════════════════════════════════════════════════════════════════════════════
// SURGICAL PROTOCOLS BY CANCER TYPE
// ═══════════════════════════════════════════════════════════════════════════════

export const SURGICAL_PROTOCOLS: Record<string, SurgicalProcedure[]> = {
  'breast': [
    {
      name: 'Breast-Conserving Surgery (Lumpectomy)',
      indication: 'Early-stage breast cancer, suitable tumor-to-breast ratio, patient preference',
      intent: 'Curative',
      approach: [
        {
          technique: 'Open',
          advantages: ['Standard approach', 'Established oncologic outcomes'],
          disadvantages: ['Larger incision than needed for tumor'],
          patientSelection: ['Most patients with unicentric disease', 'Adequate tumor-to-breast ratio']
        }
      ],
      oncologicPrinciples: [
        'Complete tumor excision with negative margins',
        'Specimen orientation for margin assessment',
        'Oncoplastic techniques for larger excisions'
      ],
      margins: {
        recommended: 'No ink on tumor (negative margin)',
        minimum: 'No ink on tumor for invasive; 2mm for DCIS',
        impactOfPositiveMargin: 'Increased local recurrence; re-excision recommended'
      },
      lymphNodeAssessment: {
        type: 'Sentinel Node',
        minimumNodes: 1,
        technique: 'Blue dye and/or radiotracer injection',
        indication: 'Clinically node-negative; if SLN positive, may avoid ALND (Z0011 criteria)'
      },
      perioperativeConsiderations: {
        preoperativeOptimization: ['Localization if non-palpable (wire, seed, radar reflector)'],
        erpsProtocol: true,
        vteProhylaxis: 'Mechanical; pharmacologic for high-risk',
        antibioticProphylaxis: 'Single dose cefazolin',
        nutritionalConsiderations: 'Standard',
        neoadjuvantOptions: 'Neoadjuvant chemotherapy to downstage for BCT',
        adjuvantOptions: 'Radiation required after BCT; systemic therapy per subtype'
      },
      outcomes: {
        mortality: '<0.1%',
        morbidity: 'Seroma 10-20%, infection 3-5%',
        hospitalStay: 'Outpatient or 23-hour observation',
        oncologicOutcome: 'Equivalent survival to mastectomy with radiation'
      }
    },
    {
      name: 'Mastectomy',
      indication: 'Multicentric disease, large tumor, BRCA carrier preference, radiation contraindicated',
      intent: 'Curative',
      approach: [
        {
          technique: 'Open',
          advantages: ['Complete removal of breast tissue'],
          disadvantages: ['Loss of breast', 'Larger surgery'],
          patientSelection: ['Patient preference', 'Not BCT candidate']
        },
        {
          technique: 'Robotic',
          advantages: ['Nipple-sparing approach', 'Smaller incision'],
          disadvantages: ['Specialized expertise required', 'Learning curve'],
          patientSelection: ['Nipple-sparing candidates', 'Immediate reconstruction planned']
        }
      ],
      oncologicPrinciples: [
        'Complete removal of all breast tissue',
        'Skin-sparing or nipple-sparing when oncologically safe',
        'Axillary assessment per protocol'
      ],
      margins: {
        recommended: 'No ink on tumor',
        minimum: 'No tumor at margin',
        impactOfPositiveMargin: 'Consider chest wall re-excision or radiation'
      },
      lymphNodeAssessment: {
        type: 'Sentinel Node',
        minimumNodes: 1,
        technique: 'Same as BCT',
        indication: 'Clinically node-negative'
      },
      perioperativeConsiderations: {
        preoperativeOptimization: ['Discuss reconstruction options', 'Genetic testing if applicable'],
        erpsProtocol: true,
        vteProhylaxis: 'Mechanical + pharmacologic if high risk',
        antibioticProphylaxis: 'Single dose cefazolin; extended if implant',
        nutritionalConsiderations: 'Standard',
        adjuvantOptions: 'Radiation if node-positive or high-risk features; systemic therapy per subtype'
      },
      outcomes: {
        mortality: '<0.5%',
        morbidity: 'Seroma 20-30%, flap necrosis 5-10%',
        hospitalStay: '1-2 days (longer with reconstruction)',
        oncologicOutcome: '10-year local recurrence <5% for node-negative'
      }
    }
  ],
  'colorectal': [
    {
      name: 'Right Hemicolectomy',
      indication: 'Right colon cancer (cecum to hepatic flexure)',
      intent: 'Curative',
      approach: [
        {
          technique: 'Laparoscopic',
          advantages: ['Faster recovery', 'Less pain', 'Equivalent oncologic outcomes'],
          disadvantages: ['Technical expertise required'],
          patientSelection: ['Most patients', 'Non-emergency']
        },
        {
          technique: 'Robotic',
          advantages: ['Improved ergonomics', 'Enhanced visualization'],
          disadvantages: ['Cost', 'Setup time'],
          patientSelection: ['Surgeon preference', 'Complex anatomy']
        },
        {
          technique: 'Open',
          advantages: ['Faster for emergencies', 'Familiar to all surgeons'],
          disadvantages: ['Longer recovery', 'More pain'],
          patientSelection: ['Emergency', 'Extensive adhesions', 'Patient factors']
        }
      ],
      oncologicPrinciples: [
        'High ligation of ileocolic and right colic vessels',
        'Complete mesocolic excision (CME)',
        'En bloc resection of tumor with adequate margins'
      ],
      margins: {
        recommended: '≥5 cm proximally and distally',
        minimum: '≥1-2 cm for colon cancer',
        impactOfPositiveMargin: 'Increased local recurrence; may need re-resection or radiation'
      },
      lymphNodeAssessment: {
        type: 'Regional Dissection',
        minimumNodes: 12,
        technique: 'Central vascular ligation with lymph node harvest',
        indication: 'All resections for cancer'
      },
      perioperativeConsiderations: {
        preoperativeOptimization: ['Bowel prep (selective)', 'Nutritional optimization'],
        erpsProtocol: true,
        vteProhylaxis: 'LMWH + mechanical',
        antibioticProphylaxis: 'Cefoxitin or cefazolin + metronidazole',
        nutritionalConsiderations: 'Early feeding; prehabilitation if malnourished',
        adjuvantOptions: 'Adjuvant chemotherapy for stage III and high-risk stage II'
      },
      outcomes: {
        mortality: '1-3%',
        morbidity: 'Anastomotic leak 2-4%, ileus 10-20%',
        hospitalStay: '4-7 days (ERAS protocol)',
        oncologicOutcome: '5-year survival: Stage I 90%, Stage II 75-80%, Stage III 50-70%'
      }
    },
    {
      name: 'Low Anterior Resection (LAR)',
      indication: 'Rectal cancer (mid to upper rectum)',
      intent: 'Curative',
      approach: [
        {
          technique: 'Laparoscopic',
          advantages: ['Better visualization of pelvis', 'Faster recovery'],
          disadvantages: ['Technical challenge in narrow pelvis'],
          patientSelection: ['Most patients']
        },
        {
          technique: 'Robotic',
          advantages: ['Improved dexterity in pelvis', 'Better nerve preservation'],
          disadvantages: ['Cost', 'Learning curve'],
          patientSelection: ['Low rectal tumors', 'Narrow pelvis']
        }
      ],
      oncologicPrinciples: [
        'Total mesorectal excision (TME)',
        'Negative circumferential resection margin (CRM)',
        'Distal margin ≥1 cm (may accept 0.5 cm for low tumors)'
      ],
      margins: {
        recommended: 'Distal 2 cm, CRM >1 mm',
        minimum: 'Distal 1 cm, CRM >1 mm',
        impactOfPositiveMargin: 'CRM+ significantly increases local recurrence'
      },
      lymphNodeAssessment: {
        type: 'Regional Dissection',
        minimumNodes: 12,
        technique: 'TME includes lymph nodes within mesorectum',
        indication: 'All rectal cancer resections'
      },
      perioperativeConsiderations: {
        preoperativeOptimization: ['MRI for staging', 'Consider stoma marking'],
        erpsProtocol: true,
        vteProhylaxis: 'Extended (4 weeks post-op)',
        antibioticProphylaxis: 'Per colorectal protocol',
        nutritionalConsiderations: 'Prehabilitation, especially if neoadjuvant therapy',
        neoadjuvantOptions: 'Total neoadjuvant therapy (TNT) for locally advanced; short-course RT or long-course CRT',
        adjuvantOptions: 'Complete TNT if not given neoadjuvantly'
      },
      outcomes: {
        mortality: '2-4%',
        morbidity: 'Anastomotic leak 5-15%, low anterior resection syndrome 50-80%',
        hospitalStay: '5-10 days',
        oncologicOutcome: '5-year local recurrence <10% with TME and neoadjuvant therapy'
      }
    }
  ],
  'lung': [
    {
      name: 'Lobectomy',
      indication: 'Early-stage NSCLC (preferred for stage I-II)',
      intent: 'Curative',
      approach: [
        {
          technique: 'Robotic',
          advantages: ['Magnified view', 'Precise dissection', 'Shorter recovery'],
          disadvantages: ['Cost', 'Requires specialized expertise'],
          patientSelection: ['Most patients with adequate pulmonary reserve']
        },
        {
          technique: 'Open',
          advantages: ['Allows tactile feedback', 'Complex cases'],
          disadvantages: ['More pain', 'Longer recovery'],
          patientSelection: ['Central tumors', 'Sleeve resections', 'Prior surgery']
        }
      ],
      oncologicPrinciples: [
        'Complete resection with negative margins',
        'Systematic mediastinal lymph node dissection',
        'En bloc resection if invasion into adjacent structures'
      ],
      margins: {
        recommended: 'Negative margin; ≥2 cm or ≥ tumor diameter',
        minimum: 'Negative margin',
        impactOfPositiveMargin: 'Consider re-resection or adjuvant radiation'
      },
      lymphNodeAssessment: {
        type: 'Regional Dissection',
        minimumNodes: 6,
        technique: 'Systematic sampling or complete mediastinal lymph node dissection',
        indication: 'All resections for cancer'
      },
      perioperativeConsiderations: {
        preoperativeOptimization: ['PFTs', 'Smoking cessation', 'Pulmonary rehabilitation'],
        erpsProtocol: true,
        vteProhylaxis: 'LMWH + mechanical',
        antibioticProphylaxis: 'Cefazolin',
        nutritionalConsiderations: 'Prehabilitation for deconditioned patients',
        adjuvantOptions: 'Adjuvant chemotherapy for stage II-III; adjuvant osimertinib for EGFR+; adjuvant atezolizumab for PD-L1 ≥1%'
      },
      outcomes: {
        mortality: '1-3%',
        morbidity: 'Air leak 10-15%, atrial fibrillation 10-20%, pneumonia 5%',
        hospitalStay: '3-5 days (VATS/robotic)',
        oncologicOutcome: '5-year survival: Stage IA 80-90%, Stage IB 70%, Stage II 50-60%'
      }
    }
  ]
};

// ═══════════════════════════════════════════════════════════════════════════════
// MULTIMODAL TREATMENT SEQUENCING
// ═══════════════════════════════════════════════════════════════════════════════

export interface MultimodalSequence {
  cancerType: string;
  stage: string;
  sequence: TreatmentPhase[];
  rationale: string;
  evidence: string;
}

export interface TreatmentPhase {
  phase: string;
  modality: 'Surgery' | 'Radiation' | 'Chemotherapy' | 'Targeted Therapy' | 'Immunotherapy' | 'Hormone Therapy';
  timing: string;
  details: string;
}

export const MULTIMODAL_SEQUENCES: MultimodalSequence[] = [
  {
    cancerType: 'Locally Advanced Rectal Cancer',
    stage: 'Stage II-III',
    sequence: [
      { phase: 'Induction', modality: 'Chemotherapy', timing: 'Weeks 1-8', details: 'FOLFOX or CAPOX x 4 cycles' },
      { phase: 'Chemoradiation', modality: 'Radiation', timing: 'Weeks 9-14', details: 'Long-course CRT (50.4 Gy + capecitabine) OR short-course RT (25 Gy/5 fx)' },
      { phase: 'Consolidation', modality: 'Chemotherapy', timing: 'Weeks 15-22', details: 'FOLFOX x 4 cycles' },
      { phase: 'Surgery', modality: 'Surgery', timing: 'Week 23-24', details: 'TME with LAR or APR' }
    ],
    rationale: 'Total neoadjuvant therapy (TNT) improves pathologic complete response and may improve survival',
    evidence: 'RAPIDO, PRODIGE 23 trials'
  },
  {
    cancerType: 'Locally Advanced NSCLC',
    stage: 'Stage IIIA-IIIB',
    sequence: [
      { phase: 'Definitive Treatment', modality: 'Radiation', timing: 'Weeks 1-6', details: 'Concurrent chemoradiation (60 Gy + platinum doublet)' },
      { phase: 'Consolidation', modality: 'Immunotherapy', timing: 'Weeks 8-60', details: 'Durvalumab x 12 months' }
    ],
    rationale: 'PACIFIC regimen is standard of care for unresectable stage III NSCLC without progression after CRT',
    evidence: 'PACIFIC trial'
  },
  {
    cancerType: 'HER2+ Breast Cancer',
    stage: 'Stage II-III',
    sequence: [
      { phase: 'Neoadjuvant', modality: 'Chemotherapy', timing: 'Weeks 1-24', details: 'AC-THP (anthracycline + taxane + trastuzumab + pertuzumab)' },
      { phase: 'Surgery', modality: 'Surgery', timing: 'Week 26-28', details: 'Lumpectomy or mastectomy + SLN biopsy' },
      { phase: 'Adjuvant RT', modality: 'Radiation', timing: 'Weeks 30-36', details: 'Whole breast/chest wall ± regional nodes' },
      { phase: 'Adjuvant HER2 Therapy', modality: 'Targeted Therapy', timing: 'Weeks 24-76', details: 'Complete 1 year of trastuzumab ± pertuzumab; T-DM1 if residual disease' }
    ],
    rationale: 'Neoadjuvant approach allows response assessment; residual disease guides adjuvant therapy',
    evidence: 'KATHERINE, APHINITY trials'
  },
  {
    cancerType: 'Esophageal/GEJ Adenocarcinoma',
    stage: 'Stage II-III',
    sequence: [
      { phase: 'Neoadjuvant', modality: 'Chemotherapy', timing: 'Weeks 1-9', details: 'CROSS regimen: Carboplatin/Paclitaxel + concurrent RT (41.4 Gy)' },
      { phase: 'Surgery', modality: 'Surgery', timing: 'Weeks 12-14', details: 'Esophagectomy' },
      { phase: 'Adjuvant IO', modality: 'Immunotherapy', timing: 'Weeks 18-70', details: 'Nivolumab x 1 year if residual disease' }
    ],
    rationale: 'Trimodality therapy standard; adjuvant nivolumab improves DFS in residual disease',
    evidence: 'CROSS trial, CheckMate 577'
  }
];

// ═══════════════════════════════════════════════════════════════════════════════
// MULTIMODAL ONCOLOGY ENGINE
// ═══════════════════════════════════════════════════════════════════════════════

export class MultimodalOncologyEngine {
  getRadiationProtocol(site: string): RadiationProtocol[] {
    return RADIATION_PROTOCOLS[site] || [];
  }

  getSurgicalProtocol(cancerType: string): SurgicalProcedure[] {
    return SURGICAL_PROTOCOLS[cancerType] || [];
  }

  getMultimodalSequence(cancerType: string, stage: string): MultimodalSequence | undefined {
    return MULTIMODAL_SEQUENCES.find(s =>
      s.cancerType.toLowerCase().includes(cancerType.toLowerCase()) &&
      s.stage.toLowerCase().includes(stage.toLowerCase())
    );
  }

  calculateBED(totalDose: number, fractions: number, alphabeta: number = 10): number {
    const dosePerFraction = totalDose / fractions;
    return totalDose * (1 + dosePerFraction / alphabeta);
  }

  assessOperability(
    performanceStatus: number,
    comorbidities: string[],
    cancerType: string
  ): {
    operable: boolean;
    approach: string;
    considerations: string[];
  } {
    const considerations: string[] = [];

    if (performanceStatus >= 3) {
      return {
        operable: false,
        approach: 'Non-surgical',
        considerations: ['Poor performance status precludes major surgery']
      };
    }

    if (comorbidities.includes('severe cardiac disease')) {
      considerations.push('Cardiology clearance required');
    }
    if (comorbidities.includes('COPD')) {
      considerations.push('Pulmonary function testing; pulmonary rehabilitation');
    }

    return {
      operable: performanceStatus <= 2,
      approach: performanceStatus === 0 ? 'Standard surgical approach' : 'Modified approach with optimization',
      considerations
    };
  }

  getAllRadiationSites(): string[] {
    return Object.keys(RADIATION_PROTOCOLS);
  }

  getAllSurgicalSites(): string[] {
    return Object.keys(SURGICAL_PROTOCOLS);
  }
}

// Export singleton
export const multimodalOncologyEngine = new MultimodalOncologyEngine();