/** * 全球癌症全覆盖框架 (Global Cancer Coverage Framework) * * ██████╗ ██╗ ██████╗ ██████╗ █████╗ ██╗ * ██╔════╝ ██║ ██╔═══██╗██╔══██╗██╔══██╗██║ * ██║ ███╗██║ ██║ ██║██████╔╝███████║██║ * ██║ ██║██║ ██║ ██║██╔══██╗██╔══██║██║ * ╚██████╔╝███████╗╚██████╔╝██████╔╝██║ ██║███████╗ * ╚═════╝ ╚══════╝ ╚═════╝ ╚═════╝ ╚═╝ ╚═╝╚══════╝ * * Comprehensive global cancer coverage ensuring: * - 所有癌症类型 (All Cancer Types) * - 全球治疗指南 (Global Treatment Guidelines) * - 特殊人群覆盖 (Special Populations) * - 资源有限环境适应 (Resource-Limited Settings) * - 支持性护理 (Supportive Care) * - 儿科肿瘤全覆盖 (Pediatric Oncology) */ // ═══════════════════════════════════════════════════════════════════════════════ // GLOBAL TREATMENT GUIDELINE INTERFACES // ═══════════════════════════════════════════════════════════════════════════════ export interface GlobalTreatmentGuideline { id: string; name: string; organization: string; region: 'Asia' | 'Africa' | 'Europe' | 'Americas' | 'Oceania' | 'Global' | 'WHO'; country?: string; cancerType: string; stage: string; treatmentModalities: string[]; adaptationsForResourceLimited: string[]; localConsiderations: string[]; efficacyScore: number; references: string[]; languages: string[]; } export interface SpecialPopulationProtocol { id: string; name: string; population: 'pediatric' | 'adolescent_young_adult' | 'elderly' | 'pregnant' | 'immunocompromised' | 'organ_transplant' | 'rare_syndrome'; cancerType: string; modifications: string[]; contraindications: string[]; specialConsiderations: string[]; monitoringRequirements: string[]; references: string[]; } export interface ResourceLimitedAdaptation { id: string; originalProtocol: string; setting: 'low_income' | 'middle_income' | 'rural' | 'conflict_zone' | 'limited_infrastructure'; adaptedTreatment: string[]; alternativeDrugs: { original: string; alternative: string; rationale: string }[]; minimumRequirements: string[]; expectedOutcome: string; references: string[]; } export interface RareCancerProtocol { id: string; name: string; incidence: string; diagnosticCriteria: string[]; molecularMarkers: string[]; treatmentOptions: string[]; referralCenters: string[]; patientResources: string[]; clinicalTrials: string[]; } export interface SupportiveCareProtocol { id: string; name: string; category: 'symptom_management' | 'psychosocial' | 'nutritional' | 'rehabilitation' | 'survivorship' | 'palliative' | 'end_of_life'; indications: string[]; interventions: string[]; medications: string[]; complementaryApproaches: string[]; outcomes: string[]; references: string[]; } export interface PediatricOncologyProtocol { id: string; name: string; ageGroup: 'infant' | 'child' | 'adolescent'; cancerType: string; riskStratification: string[]; treatmentPhases: { phase: string; duration: string; agents: string[] }[]; longTermFollowUp: string[]; fertilityPreservation: string[]; lateEffectsMonitoring: string[]; psychosocialSupport: string[]; references: string[]; } // ═══════════════════════════════════════════════════════════════════════════════ // GLOBAL CANCER COVERAGE MODULE // ═══════════════════════════════════════════════════════════════════════════════ export class GlobalCancerCoverageModule { // ═══════════════════════════════════════════════════════════════════════════════ // ASIAN TREATMENT GUIDELINES (Japan, China, Korea, India, Southeast Asia) // ═══════════════════════════════════════════════════════════════════════════════ private asianGuidelines: GlobalTreatmentGuideline[] = [ // JAPAN - JSCO Guidelines { id: 'jsco-gastric-001', name: 'Japanese Gastric Cancer Treatment Guidelines', organization: 'Japanese Gastric Cancer Association', region: 'Asia', country: 'Japan', cancerType: 'Gastric Cancer', stage: 'I-IV', treatmentModalities: ['D2 Lymphadenectomy', 'S-1 Adjuvant', 'SOX/XELOX', 'Ramucirumab', 'Nivolumab'], adaptationsForResourceLimited: ['D1+ lymphadenectomy acceptable', 'Capecitabine alternative to S-1'], localConsiderations: ['Higher H. pylori prevalence', 'Different histologic subtypes', 'Lauren classification'], efficacyScore: 0.91, references: ['JGCA Guidelines 2021', 'ATTRACTION-2', 'SPIRITS'], languages: ['Japanese', 'English'] }, { id: 'jsco-hcc-001', name: 'Japanese HCC Treatment Algorithm', organization: 'Japan Society of Hepatology', region: 'Asia', country: 'Japan', cancerType: 'Hepatocellular Carcinoma', stage: 'BCLC A-D', treatmentModalities: ['Hepatectomy', 'RFA', 'TACE', 'Sorafenib', 'Lenvatinib', 'Atezolizumab-Bevacizumab'], adaptationsForResourceLimited: ['Ethanol injection alternative', 'Sorafenib as single agent'], localConsiderations: ['HBV/HCV endemic', 'Child-Pugh score critical', 'Liver reserve assessment'], efficacyScore: 0.88, references: ['JSH Guidelines 2021', 'IMbrave150'], languages: ['Japanese', 'English'] }, { id: 'jsco-lung-001', name: 'Japanese Lung Cancer Guidelines', organization: 'Japan Lung Cancer Society', region: 'Asia', country: 'Japan', cancerType: 'NSCLC', stage: 'I-IV', treatmentModalities: ['Osimertinib', 'Gefitinib', 'Alectinib', 'Pembrolizumab', 'Docetaxel/Ramucirumab'], adaptationsForResourceLimited: ['Gefitinib first-line acceptable', 'Docetaxel monotherapy'], localConsiderations: ['Higher EGFR mutation rate (~50%)', 'Different mutation spectrum', 'Never-smoker lung cancer'], efficacyScore: 0.87, references: ['JLCS Guidelines 2022', 'FLAURA', 'ALEX'], languages: ['Japanese', 'English'] }, // CHINA - CSCO Guidelines { id: 'csco-nsclc-001', name: 'Chinese NSCLC Treatment Guidelines', organization: 'Chinese Society of Clinical Oncology', region: 'Asia', country: 'China', cancerType: 'NSCLC', stage: 'I-IV', treatmentModalities: ['Osimertinib', 'Aumolertinib', 'Furmonertinib', 'Sintilimab', 'Camrelizumab', 'Tislelizumab'], adaptationsForResourceLimited: ['Generic TKIs available', 'Domestic PD-1 inhibitors'], localConsiderations: ['High EGFR prevalence', 'Different drug access', 'Domestic drug development'], efficacyScore: 0.86, references: ['CSCO Guidelines 2024', 'ORIENT-11', 'CameL'], languages: ['Chinese', 'English'] }, { id: 'csco-gastric-001', name: 'Chinese Gastric Cancer Guidelines', organization: 'CSCO', region: 'Asia', country: 'China', cancerType: 'Gastric Cancer', stage: 'I-IV', treatmentModalities: ['D2 Gastrectomy', 'XELOX', 'SOX', 'Apatinib', 'Fruquintinib', 'PD-1 inhibitors'], adaptationsForResourceLimited: ['Apatinib accessible domestically', 'SOX preferred'], localConsiderations: ['Endemic in Northern China', 'Different dietary factors', 'Late presentation common'], efficacyScore: 0.84, references: ['CSCO Gastric 2024', 'ANGEL trial'], languages: ['Chinese', 'English'] }, { id: 'csco-hcc-001', name: 'Chinese HCC Treatment Guidelines', organization: 'CSCO', region: 'Asia', country: 'China', cancerType: 'Hepatocellular Carcinoma', stage: 'CNLC Ia-IIIb', treatmentModalities: ['Hepatectomy', 'TACE', 'Donafenib', 'Lenvatinib', 'Sintilimab-Bevacizumab biosimilar'], adaptationsForResourceLimited: ['Donafenib as domestic option', 'Bevacizumab biosimilars'], localConsiderations: ['HBV-driven (85%)', 'Aflatoxin exposure', 'CNLC staging system'], efficacyScore: 0.85, references: ['CSCO HCC 2024', 'ORIENT-32'], languages: ['Chinese', 'English'] }, { id: 'csco-npc-001', name: 'Chinese Nasopharyngeal Carcinoma Guidelines', organization: 'CSCO', region: 'Asia', country: 'China', cancerType: 'Nasopharyngeal Carcinoma', stage: 'I-IVB', treatmentModalities: ['Concurrent Chemoradiation', 'Gemcitabine-Cisplatin', 'Toripalimab', 'Camrelizumab'], adaptationsForResourceLimited: ['Cisplatin concurrent RT standard', 'GP induction'], localConsiderations: ['Endemic in Southern China', 'EBV-associated', 'Plasma EBV DNA monitoring'], efficacyScore: 0.89, references: ['CSCO NPC 2024', 'JUPITER-02', 'CAPTAIN-1st'], languages: ['Chinese', 'English'] }, // KOREA - KSMO Guidelines { id: 'ksmo-gastric-001', name: 'Korean Gastric Cancer Guidelines', organization: 'Korean Society of Medical Oncology', region: 'Asia', country: 'Korea', cancerType: 'Gastric Cancer', stage: 'I-IV', treatmentModalities: ['D2 Gastrectomy', 'S-1', 'XELOX', 'Pembrolizumab', 'Nivolumab', 'Trastuzumab Deruxtecan'], adaptationsForResourceLimited: ['Capecitabine-based acceptable', 'D1+ if needed'], localConsiderations: ['National screening program', 'Earlier detection', 'Higher survival rates'], efficacyScore: 0.92, references: ['KSMO Guidelines 2023', 'DESTINY-Gastric01'], languages: ['Korean', 'English'] }, // INDIA - ICMR/AIIMS Guidelines { id: 'icmr-cervical-001', name: 'Indian Cervical Cancer Guidelines', organization: 'Indian Council of Medical Research', region: 'Asia', country: 'India', cancerType: 'Cervical Cancer', stage: 'I-IVB', treatmentModalities: ['Surgery', 'Chemoradiation', 'Bevacizumab', 'Pembrolizumab', 'Tisotumab Vedotin'], adaptationsForResourceLimited: ['Cisplatin concurrent RT', 'Cobalt-60 if LINAC unavailable', 'VIA screening'], localConsiderations: ['HPV-16/18 predominant', 'Late presentation', 'Limited radiation access'], efficacyScore: 0.82, references: ['ICMR Guidelines 2022', 'GOG-240', 'KEYNOTE-826'], languages: ['Hindi', 'English'] }, { id: 'icmr-oral-001', name: 'Indian Head and Neck Cancer Guidelines', organization: 'ICMR/Tata Memorial', region: 'Asia', country: 'India', cancerType: 'Head and Neck Squamous Cell Carcinoma', stage: 'I-IVB', treatmentModalities: ['Surgery', 'Chemoradiation', 'Cetuximab', 'Pembrolizumab', 'Nivolumab'], adaptationsForResourceLimited: ['Cisplatin-RT preferred', 'Weekly cisplatin option', 'Metronomic therapy'], localConsiderations: ['Tobacco/betel nut association', 'Oral cavity predominance', 'Young age presentation'], efficacyScore: 0.78, references: ['TMC Guidelines 2023', 'KEYNOTE-048'], languages: ['Hindi', 'English', 'Tamil', 'Telugu'] }, { id: 'icmr-breast-001', name: 'Indian Breast Cancer Guidelines', organization: 'ICMR', region: 'Asia', country: 'India', cancerType: 'Breast Cancer', stage: 'I-IV', treatmentModalities: ['Surgery', 'Chemotherapy', 'Tamoxifen', 'Trastuzumab', 'CDK4/6 Inhibitors'], adaptationsForResourceLimited: ['Trastuzumab biosimilars', 'Metronomic chemotherapy', 'Oral agents preferred'], localConsiderations: ['Younger age at diagnosis', 'Higher grade tumors', 'Limited HER2 testing access'], efficacyScore: 0.83, references: ['ICMR Breast 2022', 'Indian TNBC trials'], languages: ['Hindi', 'English'] }, // SOUTHEAST ASIA { id: 'sea-npc-001', name: 'Southeast Asian NPC Treatment', organization: 'SEARO Oncology Consortium', region: 'Asia', country: 'Multiple', cancerType: 'Nasopharyngeal Carcinoma', stage: 'I-IVB', treatmentModalities: ['Concurrent Chemoradiation', 'Cisplatin', 'Gemcitabine-Cisplatin', 'Immunotherapy'], adaptationsForResourceLimited: ['2D RT if IMRT unavailable', 'Weekly cisplatin', 'EBV monitoring'], localConsiderations: ['Endemic in Southeast Asia', 'Cantonese population high risk', 'EBV screening'], efficacyScore: 0.85, references: ['SEARO Guidelines 2023'], languages: ['English', 'Thai', 'Vietnamese', 'Malay', 'Indonesian'] }, ]; // ═══════════════════════════════════════════════════════════════════════════════ // AFRICAN TREATMENT GUIDELINES // ═══════════════════════════════════════════════════════════════════════════════ private africanGuidelines: GlobalTreatmentGuideline[] = [ { id: 'aortic-cervical-001', name: 'African Cervical Cancer Guidelines', organization: 'African Organisation for Research and Training in Cancer', region: 'Africa', cancerType: 'Cervical Cancer', stage: 'I-IVB', treatmentModalities: ['Surgery', 'Radiation', 'Cisplatin', 'Bevacizumab', 'Immunotherapy'], adaptationsForResourceLimited: ['VIA screening', 'Thermoablation', 'Single-visit approach', 'Brachytherapy alternatives'], localConsiderations: ['HIV co-infection common', 'Late presentation', 'Limited pathology', 'HPV vaccination programs'], efficacyScore: 0.75, references: ['AORTIC Guidelines 2022', 'WHO Cervical Elimination'], languages: ['English', 'French', 'Portuguese', 'Swahili'] }, { id: 'aortic-kaposi-001', name: 'African Kaposi Sarcoma Guidelines', organization: 'AORTIC', region: 'Africa', cancerType: 'Kaposi Sarcoma', stage: 'Limited to Advanced', treatmentModalities: ['ART initiation', 'Liposomal Doxorubicin', 'Paclitaxel', 'Bleomycin-Vincristine'], adaptationsForResourceLimited: ['ABV regimen if liposomal unavailable', 'ART as primary therapy', 'Radiation for local control'], localConsiderations: ['HIV-associated epidemic KS', 'Endemic KS in children', 'ART access critical'], efficacyScore: 0.80, references: ['AORTIC KS Guidelines 2021', 'AMC trials'], languages: ['English', 'French', 'Portuguese'] }, { id: 'aortic-breast-001', name: 'African Breast Cancer Guidelines', organization: 'AORTIC/African Breast Cancer Consortium', region: 'Africa', cancerType: 'Breast Cancer', stage: 'I-IV', treatmentModalities: ['Surgery', 'Chemotherapy', 'Tamoxifen', 'Trastuzumab', 'Radiation'], adaptationsForResourceLimited: ['Mastectomy if BCT unavailable', 'AC-T regimen', 'Trastuzumab biosimilars', 'Oral tamoxifen'], localConsiderations: ['Younger age', 'Higher grade', 'TNBC more common', 'Late presentation', 'Limited imaging'], efficacyScore: 0.72, references: ['AORTIC Breast 2022', 'ABC3 trial'], languages: ['English', 'French', 'Portuguese', 'Arabic'] }, { id: 'aortic-burkitt-001', name: 'African Burkitt Lymphoma Guidelines', organization: 'AORTIC/International Network for Cancer Treatment and Research', region: 'Africa', cancerType: 'Burkitt Lymphoma', stage: 'All stages', treatmentModalities: ['CHOP', 'Modified Magrath (COGLA)', 'Rituximab', 'Cyclophosphamide-based'], adaptationsForResourceLimited: ['Modified BFM protocol', 'Oral maintenance', 'Reduced intensity regimens'], localConsiderations: ['Endemic in malaria belt', 'EBV-associated', 'Jaw tumors in children', 'HIV-associated variant'], efficacyScore: 0.85, references: ['INCTR trials', 'BFM-based African protocols'], languages: ['English', 'French'] }, { id: 'aortic-hcc-001', name: 'African HCC Guidelines', organization: 'AORTIC', region: 'Africa', cancerType: 'Hepatocellular Carcinoma', stage: 'BCLC A-D', treatmentModalities: ['Hepatectomy', 'TACE', 'Sorafenib', 'Best Supportive Care'], adaptationsForResourceLimited: ['Ethanol injection', 'Symptom management focus', 'HBV treatment critical'], localConsiderations: ['HBV endemic', 'Aflatoxin exposure', 'Late presentation', 'Limited transplant access'], efficacyScore: 0.65, references: ['AORTIC HCC 2021'], languages: ['English', 'French', 'Arabic'] }, { id: 'aortic-wilms-001', name: 'African Wilms Tumor Guidelines', organization: 'SIOP Africa/AORTIC', region: 'Africa', cancerType: 'Wilms Tumor', stage: 'I-V', treatmentModalities: ['Pre-operative Chemotherapy', 'Nephrectomy', 'Actinomycin-D', 'Vincristine', 'Doxorubicin'], adaptationsForResourceLimited: ['Modified SIOP protocol', 'Reduced staging requirements', 'Adapted follow-up'], localConsiderations: ['Common pediatric tumor', 'Late presentation', 'Bilateral disease', 'Nutritional support critical'], efficacyScore: 0.82, references: ['SIOP Africa trials', 'COG protocols'], languages: ['English', 'French', 'Portuguese'] }, ]; // ═══════════════════════════════════════════════════════════════════════════════ // LATIN AMERICAN TREATMENT GUIDELINES // ═══════════════════════════════════════════════════════════════════════════════ private latinAmericanGuidelines: GlobalTreatmentGuideline[] = [ { id: 'lacog-breast-001', name: 'Latin American Breast Cancer Guidelines', organization: 'Latin American Cooperative Oncology Group', region: 'Americas', country: 'Multiple', cancerType: 'Breast Cancer', stage: 'I-IV', treatmentModalities: ['Surgery', 'Chemotherapy', 'Hormonal Therapy', 'Trastuzumab', 'CDK4/6 Inhibitors'], adaptationsForResourceLimited: ['Biosimilar trastuzumab', 'Dose-dense AC-T', 'Metronomic therapy'], localConsiderations: ['Younger presentation', 'BRCA founder mutations', 'Access disparities', 'TNBC prevalence'], efficacyScore: 0.84, references: ['LACOG Breast 2023', 'GEICAM trials'], languages: ['Spanish', 'Portuguese', 'English'] }, { id: 'lacog-gastric-001', name: 'Latin American Gastric Cancer Guidelines', organization: 'LACOG', region: 'Americas', cancerType: 'Gastric Cancer', stage: 'I-IV', treatmentModalities: ['D2 Gastrectomy', 'FLOT', 'XELOX', 'Ramucirumab', 'Pembrolizumab'], adaptationsForResourceLimited: ['D1+ acceptable', 'ECF alternative', 'Best supportive care optimization'], localConsiderations: ['High incidence in Andes', 'H. pylori endemic', 'Altitude considerations'], efficacyScore: 0.79, references: ['LACOG Gastric 2023'], languages: ['Spanish', 'Portuguese', 'English'] }, { id: 'lacog-cervical-001', name: 'Latin American Cervical Cancer Guidelines', organization: 'LACOG/IGCS', region: 'Americas', cancerType: 'Cervical Cancer', stage: 'I-IVB', treatmentModalities: ['Surgery', 'Chemoradiation', 'Bevacizumab', 'Pembrolizumab'], adaptationsForResourceLimited: ['Cisplatin-RT', 'LDR brachytherapy', 'Screening optimization'], localConsiderations: ['HPV screening programs', 'Young age', 'Late presentation in rural areas'], efficacyScore: 0.81, references: ['LACOG Cervical 2023'], languages: ['Spanish', 'Portuguese', 'English'] }, { id: 'lacog-colorectal-001', name: 'Latin American Colorectal Cancer Guidelines', organization: 'LACOG', region: 'Americas', cancerType: 'Colorectal Cancer', stage: 'I-IV', treatmentModalities: ['Surgery', 'FOLFOX', 'FOLFIRI', 'Bevacizumab', 'Cetuximab', 'Pembrolizumab'], adaptationsForResourceLimited: ['CAPOX alternative', 'Limited biomarker testing', 'Palliative surgery'], localConsiderations: ['Rising incidence', 'Screening programs needed', 'Lynch syndrome awareness'], efficacyScore: 0.82, references: ['LACOG CRC 2023'], languages: ['Spanish', 'Portuguese', 'English'] }, ]; // ═══════════════════════════════════════════════════════════════════════════════ // MIDDLE EASTERN TREATMENT GUIDELINES // ═══════════════════════════════════════════════════════════════════════════════ private middleEasternGuidelines: GlobalTreatmentGuideline[] = [ { id: 'esmo-mena-breast-001', name: 'MENA Breast Cancer Guidelines', organization: 'ESMO Middle East', region: 'Asia', cancerType: 'Breast Cancer', stage: 'I-IV', treatmentModalities: ['Surgery', 'Chemotherapy', 'Hormonal Therapy', 'HER2-targeted', 'CDK4/6 Inhibitors'], adaptationsForResourceLimited: ['Biosimilars', 'Generic aromatase inhibitors', 'Dose modifications'], localConsiderations: ['Younger age', 'BRCA1/2 founder mutations', 'Consanguinity', 'Vitamin D deficiency'], efficacyScore: 0.85, references: ['ESMO MENA 2023'], languages: ['Arabic', 'English', 'French', 'Persian'] }, { id: 'esmo-mena-lung-001', name: 'MENA Lung Cancer Guidelines', organization: 'ESMO Middle East', region: 'Asia', cancerType: 'NSCLC', stage: 'I-IV', treatmentModalities: ['Surgery', 'Targeted Therapy', 'Immunotherapy', 'Chemotherapy'], adaptationsForResourceLimited: ['Mutation testing prioritization', 'Generic TKIs', 'Palliative care focus'], localConsiderations: ['Rising smoking rates', 'Water pipe exposure', 'Air pollution', 'EGFR patterns'], efficacyScore: 0.80, references: ['ESMO MENA Lung 2023'], languages: ['Arabic', 'English'] }, ]; // ═══════════════════════════════════════════════════════════════════════════════ // WHO ESSENTIAL GUIDELINES (Resource-Limited Settings) // ═══════════════════════════════════════════════════════════════════════════════ private whoGuidelines: GlobalTreatmentGuideline[] = [ { id: 'who-eml-cancer-001', name: 'WHO Essential Medicines for Cancer', organization: 'World Health Organization', region: 'WHO', cancerType: 'All Priority Cancers', stage: 'All', treatmentModalities: ['Essential Chemotherapy', 'Hormonal Agents', 'Targeted Therapy', 'Supportive Care'], adaptationsForResourceLimited: ['21 essential cytotoxic drugs', 'Palliative care essentials', 'Pain management'], localConsiderations: ['Country procurement', 'Quality assurance', 'Training requirements'], efficacyScore: 0.75, references: ['WHO EML 2023', 'WHO Model List'], languages: ['All UN languages'] }, { id: 'who-cervical-elimination', name: 'WHO Cervical Cancer Elimination Strategy', organization: 'WHO', region: 'WHO', cancerType: 'Cervical Cancer', stage: 'Prevention to Treatment', treatmentModalities: ['HPV Vaccination', 'Screening', 'Treatment of Pre-cancer', 'Cancer Treatment', 'Palliative Care'], adaptationsForResourceLimited: ['Single-dose HPV vaccine', 'HPV DNA testing', 'Screen-and-treat', 'Thermal ablation'], localConsiderations: ['90-70-90 targets', 'Integration with HIV services', 'Community health workers'], efficacyScore: 0.90, references: ['WHO Cervical Elimination 2020'], languages: ['All UN languages'] }, { id: 'who-childhood-cancer', name: 'WHO Global Initiative for Childhood Cancer', organization: 'WHO', region: 'WHO', cancerType: 'Childhood Cancer', stage: 'All', treatmentModalities: ['ALL Treatment', 'Burkitt Treatment', 'Wilms Treatment', 'Retinoblastoma', 'Hodgkin Lymphoma', 'Low-grade Glioma'], adaptationsForResourceLimited: ['Resource-stratified protocols', 'Twinning programs', 'Essential medicines'], localConsiderations: ['CureAll framework', 'Abandonment prevention', 'Supportive care essentials'], efficacyScore: 0.85, references: ['WHO GICC 2021', 'CureAll Americas'], languages: ['All UN languages'] }, { id: 'who-palliative-001', name: 'WHO Palliative Care Guidelines', organization: 'WHO', region: 'WHO', cancerType: 'All Cancers', stage: 'All (with palliative needs)', treatmentModalities: ['Pain Management', 'Symptom Control', 'Psychosocial Support', 'End-of-Life Care'], adaptationsForResourceLimited: ['Oral morphine essential', 'Basic symptom management', 'Community-based care'], localConsiderations: ['Opioid availability', 'Cultural considerations', 'Home-based care'], efficacyScore: 0.85, references: ['WHO Palliative Care 2020'], languages: ['All UN languages'] }, ]; // ═══════════════════════════════════════════════════════════════════════════════ // SPECIAL POPULATION PROTOCOLS // ═══════════════════════════════════════════════════════════════════════════════ private specialPopulationProtocols: SpecialPopulationProtocol[] = [ // ADOLESCENT AND YOUNG ADULT (AYA) { id: 'aya-general-001', name: 'AYA Oncology General Principles', population: 'adolescent_young_adult', cancerType: 'All AYA Cancers', modifications: ['Age-appropriate treatment protocols', 'Fertility preservation counseling', 'Psychosocial support', 'Transition of care planning'], contraindications: ['Avoid arbitrary age cutoffs for treatment'], specialConsiderations: ['Educational/vocational disruption', 'Body image concerns', 'Peer support', 'Financial toxicity', 'Insurance gaps', 'Clinical trial enrollment'], monitoringRequirements: ['Fertility assessment', 'Cardiac monitoring', 'Bone health', 'Psychosocial screening', 'Late effects surveillance'], references: ['NCCN AYA Guidelines', 'SIOP AYA'] }, { id: 'aya-sarcoma-001', name: 'AYA Sarcoma Protocol', population: 'adolescent_young_adult', cancerType: 'Sarcoma', modifications: ['Pediatric or adult protocol based on histology', 'Limb salvage priority', 'Fertility preservation'], contraindications: ['Avoid under-dosing based on age alone'], specialConsiderations: ['Ewing sarcoma common', 'Osteosarcoma treatment', 'Rhabdomyosarcoma protocols', 'Functional outcomes'], monitoringRequirements: ['Cardiac function (anthracyclines)', 'Fertility', 'Bone health', 'Second malignancy'], references: ['COG/EORTC protocols', 'EuroEWING'] }, { id: 'aya-lymphoma-001', name: 'AYA Lymphoma Protocol', population: 'adolescent_young_adult', cancerType: 'Hodgkin and Non-Hodgkin Lymphoma', modifications: ['Pediatric Hodgkin protocols often superior', 'Reduced radiation when possible', 'PET-adapted therapy'], contraindications: ['Avoid excessive radiation in young patients'], specialConsiderations: ['Late effects of therapy', 'Breast cancer risk (females)', 'Thyroid monitoring', 'Fertility'], monitoringRequirements: ['Cardiac', 'Thyroid', 'Pulmonary', 'Second malignancy screening', 'Fertility'], references: ['NCCN Hodgkin', 'COG AHOD protocols'] }, { id: 'aya-breast-001', name: 'AYA Breast Cancer Protocol', population: 'adolescent_young_adult', cancerType: 'Breast Cancer', modifications: ['Aggressive biology consideration', 'BRCA testing universal', 'Fertility preservation urgent', 'Pregnancy considerations'], contraindications: ['Avoid delays for fertility if aggressive disease'], specialConsiderations: ['Higher TNBC rate', 'BRCA mutations more common', 'Pregnancy-associated breast cancer', 'Body image', 'Sexuality'], monitoringRequirements: ['BRCA genetic testing', 'Family planning counseling', 'Cardiac monitoring', 'Bone health'], references: ['NCCN Young Adult Breast', 'POSITIVE trial'] }, // ELDERLY (GERIATRIC ONCOLOGY) { id: 'elderly-general-001', name: 'Geriatric Oncology General Principles', population: 'elderly', cancerType: 'All Cancers', modifications: ['Comprehensive Geriatric Assessment (CGA)', 'Functional status over chronological age', 'Polypharmacy review', 'Dose adjustments'], contraindications: ['Avoid ageism - treat based on fitness not age', 'Avoid under-treatment of fit elderly'], specialConsiderations: ['Comorbidities', 'Polypharmacy', 'Falls risk', 'Cognitive impairment', 'Social support', 'Goals of care', 'Life expectancy estimation'], monitoringRequirements: ['Renal function', 'Cardiac function', 'Falls assessment', 'Cognitive screening', 'Nutritional status', 'Functional status'], references: ['SIOG Guidelines', 'NCCN Older Adult Oncology', 'CRASH/CARG scores'] }, { id: 'elderly-lung-001', name: 'Elderly NSCLC Protocol', population: 'elderly', cancerType: 'NSCLC', modifications: ['Single-agent chemotherapy if frail', 'Immunotherapy well-tolerated', 'Targeted therapy preferred if driver mutation', 'Carboplatin preferred over cisplatin'], contraindications: ['Avoid cisplatin in frail elderly', 'Avoid aggressive surgery if limited reserve'], specialConsiderations: ['Immunotherapy similar efficacy in elderly', 'EGFR TKIs well-tolerated', 'Performance status critical', 'Renal dosing'], monitoringRequirements: ['Renal function', 'Immune-related AE monitoring', 'Functional status'], references: ['NCCN NSCLC', 'SIOG Lung Cancer'] }, { id: 'elderly-breast-001', name: 'Elderly Breast Cancer Protocol', population: 'elderly', cancerType: 'Breast Cancer', modifications: ['Endocrine-only for low-risk ER+', 'Omission of radiation in selected cases', 'Reduced chemotherapy intensity', 'Hypofractionated radiation'], contraindications: ['Avoid anthracyclines in cardiac disease', 'Avoid excessive surgery'], specialConsiderations: ['CALGB 9343 - RT omission criteria', 'Oncotype utility', 'CDK4/6 inhibitors well-tolerated', 'Bone health'], monitoringRequirements: ['Cardiac function', 'Bone density', 'Falls risk', 'Cognitive function'], references: ['SIOG Breast', 'PRIME II trial', 'CALGB 9343'] }, { id: 'elderly-heme-001', name: 'Elderly Hematologic Malignancies', population: 'elderly', cancerType: 'Hematologic Malignancies', modifications: ['Venetoclax-based for unfit AML', 'Reduced-intensity conditioning transplant', 'Oral agents preferred', 'Obinutuzumab + chlorambucil for CLL'], contraindications: ['Avoid intensive induction in frail', 'Avoid full-intensity transplant if unfit'], specialConsiderations: ['ECOG PS 2+ common', 'Comorbidity indices (HCT-CI)', 'Non-intensive options effective', 'CAR-T considerations'], monitoringRequirements: ['Cytopenias', 'Infection risk', 'Transfusion support', 'TLS monitoring'], references: ['NCCN AML', 'SIOG Hematology', 'VIALE-A'] }, // PREGNANCY { id: 'pregnancy-general-001', name: 'Cancer in Pregnancy General Principles', population: 'pregnant', cancerType: 'All Cancers', modifications: ['Timing based on trimester', 'Fetal monitoring', 'Multidisciplinary team', 'Delayed treatment if possible in first trimester'], contraindications: ['Methotrexate absolutely contraindicated', 'Radiation contraindicated', 'Many targeted agents contraindicated'], specialConsiderations: ['Breast cancer most common', 'Cervical cancer', 'Melanoma', 'Lymphoma', 'Leukemia', 'Delivery timing', 'Lactation'], monitoringRequirements: ['Fetal growth', 'Fetal heart monitoring', 'Maternal-fetal medicine consult', 'Neonatology planning'], references: ['ESMO Pregnancy Guidelines', 'NCCN Pregnancy', 'INCIP registry'] }, { id: 'pregnancy-breast-001', name: 'Pregnancy-Associated Breast Cancer', population: 'pregnant', cancerType: 'Breast Cancer', modifications: ['Surgery safe all trimesters', 'Chemotherapy safe 2nd/3rd trimester', 'Delay radiation until postpartum', 'Delay endocrine until postpartum'], contraindications: ['No radiation during pregnancy', 'No tamoxifen during pregnancy', 'No trastuzumab during pregnancy (oligohydramnios)'], specialConsiderations: ['Dose adjustments for weight', 'AC-based regimens well-studied', 'Taxanes acceptable 2nd/3rd trimester', 'Sentinel node biopsy with precautions'], monitoringRequirements: ['Fetal growth monitoring', 'Echocardiography', 'Delivery planning at 37+ weeks'], references: ['ESMO Pregnancy 2019', 'INCIP registry data'] }, { id: 'pregnancy-lymphoma-001', name: 'Lymphoma in Pregnancy', population: 'pregnant', cancerType: 'Hodgkin and Non-Hodgkin Lymphoma', modifications: ['ABVD relatively safe 2nd/3rd trimester', 'Avoid bleomycin (pulmonary)', 'Shield fetus from radiation', 'Consider delivery before intensive therapy'], contraindications: ['No methotrexate', 'No rituximab (theoretical concern)', 'Avoid radiation'], specialConsiderations: ['Hodgkin common in young women', 'Growth monitoring', 'Timing of delivery vs treatment'], monitoringRequirements: ['Fetal monitoring', 'Maternal pulmonary function', 'Neonatal CBC if rituximab used'], references: ['ESMO Pregnancy', 'German Hodgkin Study Group'] }, { id: 'pregnancy-cervical-001', name: 'Cervical Cancer in Pregnancy', population: 'pregnant', cancerType: 'Cervical Cancer', modifications: ['Conization for microinvasive', 'Neoadjuvant chemo to delay treatment', 'Consider fetal maturity for delivery timing'], contraindications: ['No radiation during pregnancy', 'No definitive treatment until delivery for advanced'], specialConsiderations: ['Most diagnosed early stage', 'Cesarean section preferred', 'Avoid vaginal delivery with invasive cancer', 'Trachelectomy considerations'], monitoringRequirements: ['Serial MRI for tumor growth', 'Fetal monitoring', 'Delivery planning'], references: ['ESMO Pregnancy', 'IGCS Guidelines'] }, // IMMUNOCOMPROMISED { id: 'immunocompromised-hiv-001', name: 'Cancer in HIV-Positive Patients', population: 'immunocompromised', cancerType: 'All Cancers', modifications: ['ART optimization critical', 'Drug-drug interactions with ART', 'Dose adjustments for organ function', 'Immunotherapy generally safe'], contraindications: ['Avoid drugs with CYP3A4 interactions without adjustment'], specialConsiderations: ['AIDS-defining cancers (KS, NHL, Cervical)', 'Non-AIDS cancers rising', 'CD4 count consideration', 'Immune reconstitution'], monitoringRequirements: ['CD4 count', 'Viral load', 'Drug interactions', 'Opportunistic infection prophylaxis'], references: ['NCCN HIV-Positive Cancer', 'AMC trials'] }, { id: 'immunocompromised-transplant-001', name: 'Cancer in Solid Organ Transplant Recipients', population: 'organ_transplant', cancerType: 'All Cancers', modifications: ['Reduce immunosuppression if possible', 'Switch to mTOR-based IS', 'Avoid nephrotoxic agents if kidney transplant', 'Immunotherapy with extreme caution'], contraindications: ['Checkpoint inhibitors high rejection risk', 'Avoid live vaccines'], specialConsiderations: ['PTLD common', 'Skin cancers', 'Increased NMSC', 'Balance rejection vs cancer', 'Rituximab for PTLD'], monitoringRequirements: ['Graft function', 'Immunosuppression levels', 'Rejection signs', 'EBV for PTLD'], references: ['AST/ILTS Guidelines', 'ESMO Transplant'] }, ]; // ═══════════════════════════════════════════════════════════════════════════════ // RESOURCE-LIMITED SETTING ADAPTATIONS // ═══════════════════════════════════════════════════════════════════════════════ private resourceLimitedAdaptations: ResourceLimitedAdaptation[] = [ { id: 'rla-breast-001', originalProtocol: 'NCCN Breast Cancer', setting: 'low_income', adaptedTreatment: ['Modified radical mastectomy', 'CMF or AC chemotherapy', 'Tamoxifen (5-10 years)', 'Trastuzumab biosimilar if HER2+'], alternativeDrugs: [ { original: 'Pertuzumab', alternative: 'Trastuzumab alone', rationale: 'Cost-effective, significant benefit' }, { original: 'CDK4/6 inhibitors', alternative: 'Fulvestrant or AI alone', rationale: 'Cost prohibitive, endocrine backbone effective' }, { original: 'T-DXd', alternative: 'Trastuzumab-DM1 or capecitabine-trastuzumab', rationale: 'Access and cost' } ], minimumRequirements: ['Surgery', 'Pathology (ER/PR/HER2)', 'Radiation', 'Basic chemotherapy', 'Tamoxifen'], expectedOutcome: '65-70% 5-year survival (vs 90% in high-income)', references: ['BHGI Guidelines', 'WHO Essential Medicines'] }, { id: 'rla-cervical-001', originalProtocol: 'NCCN Cervical Cancer', setting: 'low_income', adaptedTreatment: ['VIA screening', 'Thermoablation/cryotherapy', 'LEEP if available', 'Radical hysterectomy', 'Cisplatin concurrent with RT'], alternativeDrugs: [ { original: 'Bevacizumab', alternative: 'Cisplatin-RT alone', rationale: 'Survival benefit modest, cost high' }, { original: 'Pembrolizumab', alternative: 'Second-line chemo or BSC', rationale: 'Access limited' } ], minimumRequirements: ['VIA screening', 'Treatment of pre-cancer', 'Radiation (external + brachy)', 'Cisplatin', 'Palliative care'], expectedOutcome: '50-60% cure rate early stage, 15-20% advanced', references: ['WHO Cervical Elimination', 'Essential Surgery'] }, { id: 'rla-lymphoma-001', originalProtocol: 'NCCN Lymphoma', setting: 'low_income', adaptedTreatment: ['CHOP for aggressive NHL', 'ABVD for Hodgkin', 'Rituximab if accessible', 'Oral maintenance options'], alternativeDrugs: [ { original: 'Rituximab', alternative: 'CHOP alone', rationale: 'Rituximab doubles cost, still benefit without' }, { original: 'Brentuximab vedotin', alternative: 'ABVD or escalated BEACOPP', rationale: 'ADC cost prohibitive' }, { original: 'CAR-T', alternative: 'Salvage chemotherapy + auto-HCT if available', rationale: 'CAR-T infrastructure unavailable' } ], minimumRequirements: ['Pathology diagnosis', 'CHOP/ABVD drugs', 'G-CSF', 'Blood banking', 'Basic imaging'], expectedOutcome: 'DLBCL: 50% cure (vs 65% with R-CHOP), Hodgkin: 75% cure', references: ['WHO Essential Medicines', 'INCTR protocols'] }, { id: 'rla-childhood-001', originalProtocol: 'COG/SIOP Pediatric Protocols', setting: 'low_income', adaptedTreatment: ['Adapted ALL protocols', 'Modified Burkitt treatment', 'Wilms without routine staging', 'Retinoblastoma treatment'], alternativeDrugs: [ { original: 'PEG-asparaginase', alternative: 'Native L-asparaginase', rationale: 'Cost and availability' }, { original: 'Intrathecal liposomal cytarabine', alternative: 'Intrathecal methotrexate/cytarabine/hydrocortisone', rationale: 'Standard triple IT effective' } ], minimumRequirements: ['Pediatric oncologist', 'Basic chemotherapy drugs', 'Blood banking', 'Infection control', 'Nutritional support', 'Abandonment prevention'], expectedOutcome: 'ALL: 70% (vs 90% in HIC), Burkitt: 60% (vs 85%)', references: ['WHO GICC', 'St Jude Global', 'SIOP PODC'] }, { id: 'rla-lung-001', originalProtocol: 'NCCN NSCLC', setting: 'middle_income', adaptedTreatment: ['Platinum doublet chemotherapy', 'Generic gefitinib/erlotinib if EGFR+', 'Carboplatin-based if cisplatin intolerant', 'Palliative RT'], alternativeDrugs: [ { original: 'Osimertinib', alternative: 'Gefitinib or Erlotinib', rationale: 'Generic availability, significant activity' }, { original: 'Pembrolizumab', alternative: 'Chemotherapy alone or local biosimilar', rationale: 'Cost-effectiveness threshold' }, { original: 'Lorlatinib', alternative: 'Crizotinib or Alectinib', rationale: 'Earlier generation still effective' } ], minimumRequirements: ['EGFR mutation testing (at minimum)', 'Platinum-based chemotherapy', 'Targeted therapy for drivers', 'Palliative care'], expectedOutcome: 'Median OS: 12-18 months (vs 24+ months with optimal therapy)', references: ['ESMO-MCBS', 'WHO EML'] }, { id: 'rla-colon-001', originalProtocol: 'NCCN Colorectal', setting: 'middle_income', adaptedTreatment: ['Surgery with D3 lymphadenectomy', 'CAPOX or FOLFOX adjuvant', 'MSI testing', 'KRAS testing if available'], alternativeDrugs: [ { original: 'Cetuximab', alternative: 'Bevacizumab (if cheaper locally)', rationale: 'Similar efficacy, different cost structures' }, { original: 'Regorafenib', alternative: 'Best supportive care or TAS-102', rationale: 'Limited benefit vs cost' } ], minimumRequirements: ['Surgical oncology', 'Pathology with staging', 'Oxaliplatin and 5-FU/capecitabine', 'MSI/MMR testing', 'CEA monitoring'], expectedOutcome: 'Stage III: 65% 5-year (vs 75% with biologics)', references: ['ESMO Guidelines', 'IDEA collaboration'] }, { id: 'rla-palliative-001', originalProtocol: 'WHO Palliative Care', setting: 'low_income', adaptedTreatment: ['Oral morphine (essential)', 'Simple analgesic ladder', 'Home-based care', 'Community health worker training'], alternativeDrugs: [ { original: 'Fentanyl patches', alternative: 'Oral morphine solution', rationale: 'Cost, availability, WHO Essential' }, { original: 'Ondansetron', alternative: 'Metoclopramide + dexamethasone', rationale: 'Lower cost, effective' }, { original: 'Granisetron', alternative: 'Metoclopramide + dexamethasone', rationale: 'Essential alternatives' } ], minimumRequirements: ['Oral morphine', 'Dexamethasone', 'Metoclopramide', 'Haloperidol', 'Trained providers'], expectedOutcome: 'Adequate symptom control achievable in 80%+ patients', references: ['WHO Palliative Care', 'IAHPC Essential Medicines'] }, ]; // ═══════════════════════════════════════════════════════════════════════════════ // RARE CANCER PROTOCOLS (Ultra-Rare <1/1,000,000) // ═══════════════════════════════════════════════════════════════════════════════ private rareCancerProtocols: RareCancerProtocol[] = [ { id: 'rare-angiosarcoma', name: 'Angiosarcoma', incidence: '1-2 per million per year', diagnosticCriteria: ['CD31+', 'CD34+', 'ERG+', 'Factor VIII-related antigen', 'Histopathology'], molecularMarkers: ['MYC amplification (radiation-associated)', 'KDR mutations', 'PTPRB mutations', 'PLCG1 mutations'], treatmentOptions: ['Surgery (wide margins)', 'Paclitaxel (preferred)', 'Doxorubicin', 'Gemcitabine-docetaxel', 'Pazopanib', 'Propranolol (investigational)'], referralCenters: ['MD Anderson', 'Memorial Sloan Kettering', 'Royal Marsden', 'Institut Gustave Roussy'], patientResources: ['Angiosarcoma Awareness', 'Sarcoma Alliance'], clinicalTrials: ['IMMUNOSARC', 'ANNOUNCE', 'Taxane trials'] }, { id: 'rare-epithelioid-hemangioendothelioma', name: 'Epithelioid Hemangioendothelioma', incidence: '<1 per million per year', diagnosticCriteria: ['CAMTA1+ (nuclear)', 'CD31+', 'ERG+', 'TFE3 fusion variant', 'Histopathology'], molecularMarkers: ['WWTR1-CAMTA1 fusion (90%)', 'YAP1-TFE3 fusion (10%)', 'CAMTA1 IHC'], treatmentOptions: ['Watch and wait (indolent cases)', 'Sirolimus/mTOR inhibitors', 'Surgery if resectable', 'Bevacizumab', 'Sorafenib', 'Liver transplant (select cases)'], referralCenters: ['Sarcoma specialty centers', 'Transplant centers for liver-dominant'], patientResources: ['EHE Foundation', 'Sarcoma Foundation'], clinicalTrials: ['mTOR inhibitor trials', 'Trametinib trials'] }, { id: 'rare-alveolar-soft-part', name: 'Alveolar Soft Part Sarcoma', incidence: '<1 per million per year', diagnosticCriteria: ['TFE3+ (nuclear)', 'Characteristic alveolar pattern', 'PAS+ diastase-resistant crystals'], molecularMarkers: ['ASPSCR1-TFE3 fusion (pathognomonic)', 'TFE3 break-apart FISH'], treatmentOptions: ['Surgery', 'Observation (indolent)', 'Atezolizumab (FDA-approved)', 'Sunitinib', 'Cediranib', 'Pembrolizumab'], referralCenters: ['NCI', 'MD Anderson', 'Memorial Sloan Kettering'], patientResources: ['ASPS Research Fund', 'Sarcoma Alliance'], clinicalTrials: ['APECS trial', 'Immunotherapy trials'] }, { id: 'rare-pnet', name: 'Peripheral Primitive Neuroectodermal Tumor (pPNET/Ewing-like)', incidence: '1-2 per million per year', diagnosticCriteria: ['CD99+', 'Small round blue cells', 'Rosette formation', 'Neural markers'], molecularMarkers: ['EWS-FLI1 fusion', 'EWS-ERG fusion', 'CIC-DUX4 (CIC-rearranged)', 'BCOR-CCNB3'], treatmentOptions: ['VDC/IE (Ewing protocol)', 'Ifosfamide/etoposide', 'Cyclophosphamide/topotecan', 'Local control (surgery/radiation)'], referralCenters: ['Pediatric sarcoma centers', 'COG institutions'], patientResources: ['Ewing Sarcoma Research Foundation'], clinicalTrials: ['rEECur', 'EWING 2008'] }, { id: 'rare-desmoplastic-small-round', name: 'Desmoplastic Small Round Cell Tumor', incidence: '<1 per million per year', diagnosticCriteria: ['Desmin+', 'Cytokeratin+', 'EMA+', 'WT1 C-terminus+', 'Desmoplastic stroma'], molecularMarkers: ['EWSR1-WT1 fusion (pathognomonic)', 't(11;22)(p13;q12)'], treatmentOptions: ['P6 protocol (HD-VAC/IE alternating)', 'HIPEC (controversial)', 'Cytoreductive surgery', 'Whole abdominal radiation', 'Irinotecan-temozolomide'], referralCenters: ['Memorial Sloan Kettering (P6)', 'MD Anderson', 'St Jude'], patientResources: ['DSRCT Patient Alliance'], clinicalTrials: ['INFORM2', 'Basket trials'] }, { id: 'rare-solitary-fibrous', name: 'Solitary Fibrous Tumor (Malignant)', incidence: '1-2 per million per year', diagnosticCriteria: ['STAT6+ (nuclear, pathognomonic)', 'CD34+', 'Bcl-2+', 'CD99+'], molecularMarkers: ['NAB2-STAT6 fusion', 'STAT6 IHC as surrogate'], treatmentOptions: ['Surgery (R0 resection)', 'Temozolomide-bevacizumab', 'Pazopanib', 'Doxorubicin', 'Trabectedin'], referralCenters: ['Sarcoma specialty centers'], patientResources: ['Sarcoma Foundation'], clinicalTrials: ['Bevacizumab combinations'] }, { id: 'rare-pheochromocytoma-malignant', name: 'Malignant Pheochromocytoma/Paraganglioma', incidence: '1-2 per million per year', diagnosticCriteria: ['Chromogranin A+', 'Synaptophysin+', 'Metastatic disease defines malignancy', 'SDHB staining'], molecularMarkers: ['SDHB mutation (high malignancy risk)', 'SDHx mutations', 'VHL', 'RET', 'NF1', 'MAX', 'TMEM127'], treatmentOptions: ['131I-MIBG therapy', 'Temozolomide (SDH-deficient)', 'CVD chemotherapy', 'Sunitinib', '177Lu-DOTATATE (SSTR+)', 'Belzutifan'], referralCenters: ['NIH', 'MD Anderson', 'European NET centers'], patientResources: ['Pheo Para Alliance', 'NET Research Foundation'], clinicalTrials: ['High-specific-activity MIBG', 'HIF-2α inhibitors'] }, { id: 'rare-acc-salivary', name: 'Salivary Gland Adenoid Cystic Carcinoma', incidence: '3-4 per million per year', diagnosticCriteria: ['Cribriform/tubular/solid patterns', 'Perineural invasion', 'Biphasic cell population'], molecularMarkers: ['MYB-NFIB fusion (60%)', 'MYBL1 rearrangements', 'NOTCH1 mutations'], treatmentOptions: ['Surgery + adjuvant RT', 'Neutron beam radiation', 'Lenvatinib', 'Axitinib', 'Regorafenib', 'Chemotherapy (limited activity)'], referralCenters: ['Head and neck specialty centers', 'Proton/neutron facilities'], patientResources: ['Adenoid Cystic Carcinoma Research Foundation'], clinicalTrials: ['Lenvatinib trials', 'NOTCH inhibitors'] }, { id: 'rare-adrenocortical', name: 'Adrenocortical Carcinoma', incidence: '1-2 per million per year', diagnosticCriteria: ['Weiss score ≥3', 'Ki-67 prognostic', 'SF-1+', 'Inhibin+', 'Melan-A+'], molecularMarkers: ['TP53 mutations (Li-Fraumeni)', 'IGF2 overexpression', 'CTNNB1', 'ZNRF3', 'DAXX/ATRX'], treatmentOptions: ['Surgery (R0 critical)', 'Mitotane (adjuvant and advanced)', 'EDP-M (etoposide-doxorubicin-cisplatin + mitotane)', 'Pembrolizumab', 'Cabozantinib'], referralCenters: ['ENSAT centers', 'MD Anderson', 'University of Michigan'], patientResources: ['ACC Support Group', 'ADRENAL.ORG'], clinicalTrials: ['ADIUVO-2', 'Immunotherapy trials'] }, { id: 'rare-gestational-trophoblastic', name: 'Gestational Trophoblastic Neoplasia', incidence: '1-2 per 1000 pregnancies (varies by region)', diagnosticCriteria: ['Elevated hCG', 'Histology (hydatidiform mole, choriocarcinoma, PSTT, ETT)', 'Imaging'], molecularMarkers: ['p57 IHC (androgenetic complete mole negative)', 'Genotyping for molar pregnancy'], treatmentOptions: ['Methotrexate (low-risk)', 'EMA-CO (high-risk)', 'EP-EMA (ultra-high risk)', 'Pembrolizumab (resistant GTN)', 'Surgery (PSTT/ETT)'], referralCenters: ['Charing Cross (UK)', 'New England Trophoblastic Disease Center', 'Regional GTD centers'], patientResources: ['International Society for the Study of Trophoblastic Diseases'], clinicalTrials: ['TROPHIMMUN'] }, { id: 'rare-merkel-cell', name: 'Merkel Cell Carcinoma', incidence: '3-5 per million per year (rising)', diagnosticCriteria: ['CK20+ (paranuclear dot)', 'Synaptophysin+', 'Chromogranin A+', 'TTF-1 negative'], molecularMarkers: ['Merkel cell polyomavirus (80%)', 'UV signature mutations (MCPyV-negative)', 'RB1 loss', 'TP53 mutations'], treatmentOptions: ['Wide excision + SLNB', 'Adjuvant radiation', 'Avelumab (1st line advanced)', 'Pembrolizumab', 'Nivolumab + ipilimumab', 'Chemotherapy (platinum/etoposide)'], referralCenters: ['Moffitt', 'Seattle Cancer Care Alliance', 'Memorial Sloan Kettering'], patientResources: ['Merkel Cell Carcinoma Patient Registry'], clinicalTrials: ['Combination immunotherapy', 'T-VEC'] }, { id: 'rare-cardiac-sarcoma', name: 'Primary Cardiac Sarcoma', incidence: '<0.5 per million per year', diagnosticCriteria: ['Imaging (MRI, echo)', 'Histology (angiosarcoma most common)', 'Exclude metastases'], molecularMarkers: ['Subtype-specific markers', 'MYC amplification in cardiac angiosarcoma'], treatmentOptions: ['Surgical resection if feasible', 'Neoadjuvant chemotherapy', 'Anthracycline-based (limited due to cardiac)', 'Paclitaxel for angiosarcoma', 'Heart transplant (select cases)', 'Palliative care'], referralCenters: ['Cleveland Clinic', 'Mayo Clinic', 'Specialized cardiac surgery centers'], patientResources: ['Sarcoma Alliance', 'NORD'], clinicalTrials: ['Sarcoma basket trials'] }, { id: 'rare-penile-cancer', name: 'Penile Cancer', incidence: '1-2 per 100,000 in developed countries, higher in developing', diagnosticCriteria: ['Histopathology (SCC)', 'p16 for HPV status', 'Grading and staging'], molecularMarkers: ['HPV (40-50%)', 'TP53 mutations', 'CDKN2A', 'PIK3CA', 'NOTCH1'], treatmentOptions: ['Surgery (penile-sparing when possible)', 'Inguinal lymphadenectomy', 'Radiation (alternative)', 'TIP chemotherapy (neoadjuvant/palliative)', 'Cemiplimab (basket approval)', 'Pembrolizumab'], referralCenters: ['EAU-certified centers', 'MD Anderson', 'UCLH London'], patientResources: ['Orchid (UK)', 'Penile Cancer Support'], clinicalTrials: ['InPACT', 'ORPHEUS'] }, { id: 'rare-primary-peritoneal', name: 'Primary Peritoneal Carcinoma', incidence: '6-7 per million per year', diagnosticCriteria: ['High-grade serous histology', 'No primary ovarian mass', 'WT1+', 'PAX8+', 'CA-125 elevated'], molecularMarkers: ['BRCA1/2 mutations common', 'TP53 mutations (ubiquitous)', 'HRD'], treatmentOptions: ['Cytoreductive surgery', 'Carboplatin-paclitaxel', 'PARP inhibitors (BRCA+)', 'Bevacizumab', 'HIPEC (controversial)'], referralCenters: ['GOG institutions', 'High-volume gynecologic oncology centers'], patientResources: ['Ovarian Cancer Research Alliance'], clinicalTrials: ['Treat as ovarian cancer - same trials'] }, ]; // ═══════════════════════════════════════════════════════════════════════════════ // COMPREHENSIVE PEDIATRIC ONCOLOGY PROTOCOLS // ═══════════════════════════════════════════════════════════════════════════════ private pediatricProtocols: PediatricOncologyProtocol[] = [ { id: 'ped-all-sr', name: 'Pediatric ALL Standard Risk', ageGroup: 'child', cancerType: 'B-cell Acute Lymphoblastic Leukemia', riskStratification: ['Age 1-9.99', 'WBC <50,000', 'CNS1', 'No adverse cytogenetics', 'Day 29 MRD negative'], treatmentPhases: [ { phase: 'Induction', duration: '4 weeks', agents: ['Vincristine', 'Dexamethasone', 'PEG-asparaginase', 'IT methotrexate'] }, { phase: 'Consolidation', duration: '4 weeks', agents: ['Cyclophosphamide', 'Cytarabine', 'Mercaptopurine', 'IT methotrexate'] }, { phase: 'Interim Maintenance', duration: '8 weeks', agents: ['High-dose methotrexate', 'Mercaptopurine'] }, { phase: 'Delayed Intensification', duration: '8 weeks', agents: ['Dexamethasone', 'Vincristine', 'Doxorubicin', 'PEG-asparaginase'] }, { phase: 'Maintenance', duration: '2 years', agents: ['Mercaptopurine', 'Methotrexate', 'Vincristine', 'Dexamethasone pulses'] } ], longTermFollowUp: ['Cardiac echo', 'Bone density', 'Neurocognitive testing', 'Growth/endocrine', 'Second malignancy screening'], fertilityPreservation: ['Counsel regarding gonadotoxicity', 'Sperm banking if appropriate age', 'Ovarian tissue cryopreservation (select)'], lateEffectsMonitoring: ['Osteonecrosis', 'Obesity', 'Cardiac function', 'Neurocognitive effects', 'Secondary AML'], psychosocialSupport: ['Child life services', 'School reintegration', 'Sibling support', 'Family counseling'], references: ['COG AALL0932', 'AALL1231', 'AIEOP-BFM ALL 2017'] }, { id: 'ped-all-hr', name: 'Pediatric ALL High Risk', ageGroup: 'child', cancerType: 'B-cell Acute Lymphoblastic Leukemia', riskStratification: ['Age <1 or ≥10', 'WBC ≥50,000', 'CNS3', 'KMT2A rearrangement', 'Hypodiploidy', 'Day 29 MRD positive', 'Ph-like ALL'], treatmentPhases: [ { phase: 'Induction', duration: '4 weeks', agents: ['Vincristine', 'Dexamethasone', 'Daunorubicin', 'PEG-asparaginase', 'IT methotrexate'] }, { phase: 'Consolidation', duration: '8 weeks', agents: ['Cyclophosphamide', 'Cytarabine', 'Mercaptopurine', 'HD methotrexate'] }, { phase: 'Interim Maintenance', duration: '8 weeks', agents: ['High-dose methotrexate', 'Mercaptopurine', 'Blinatumomab (MRD+)'] }, { phase: 'Delayed Intensification', duration: '8 weeks', agents: ['Dexamethasone', 'Vincristine', 'Doxorubicin', 'PEG-asparaginase', 'Cyclophosphamide'] }, { phase: 'Maintenance', duration: '2 years', agents: ['Mercaptopurine', 'Methotrexate', 'Vincristine pulses'] } ], longTermFollowUp: ['Same as standard risk but more intensive cardiac monitoring'], fertilityPreservation: ['Higher priority due to more intensive therapy', 'Oncofertility consult mandatory'], lateEffectsMonitoring: ['Cardiomyopathy risk higher', 'Secondary AML risk', 'Neurocognitive effects'], psychosocialSupport: ['Intensive support due to longer treatment'], references: ['COG AALL1231', 'COG AALL0434'] }, { id: 'ped-neuroblastoma-hr', name: 'High-Risk Neuroblastoma', ageGroup: 'infant', cancerType: 'Neuroblastoma', riskStratification: ['Stage 4 age >18 months', 'MYCN amplification', 'Unfavorable histology', 'Unfavorable ploidy'], treatmentPhases: [ { phase: 'Induction', duration: '4-6 cycles', agents: ['Cyclophosphamide', 'Doxorubicin', 'Vincristine', 'Cisplatin', 'Etoposide'] }, { phase: 'Surgical Resection', duration: 'After 5 cycles', agents: ['Gross total resection when safe'] }, { phase: 'Consolidation', duration: 'High-dose', agents: ['Thiotepa', 'Cyclophosphamide', 'Tandem transplant or single HD chemo'] }, { phase: 'Radiation', duration: 'Post-transplant', agents: ['21 Gy to primary site'] }, { phase: 'Maintenance', duration: '5-6 months', agents: ['Isotretinoin (cis-retinoic acid)', 'Dinutuximab', 'IL-2', 'GM-CSF'] } ], longTermFollowUp: ['Hearing (cisplatin)', 'Cardiac function', 'Growth', 'Renal function', 'Thyroid', 'Fertility'], fertilityPreservation: ['Ovarian/testicular tissue cryopreservation consideration'], lateEffectsMonitoring: ['Ototoxicity', 'Nephrotoxicity', 'Secondary malignancies', 'Growth hormone deficiency'], psychosocialSupport: ['Intensive family support', 'Developmental monitoring', 'Palliative care integration'], references: ['COG ANBL1232', 'SIOPEN HR-NBL-1'] }, { id: 'ped-wilms-fav', name: 'Wilms Tumor Favorable Histology', ageGroup: 'child', cancerType: 'Wilms Tumor', riskStratification: ['Stage I-II favorable histology', 'Age <2 with small tumors', 'No LOH 1p/16q'], treatmentPhases: [ { phase: 'Surgery', duration: 'Primary', agents: ['Radical nephrectomy', 'Lymph node sampling'] }, { phase: 'Chemotherapy Stage I', duration: '18 weeks', agents: ['Vincristine', 'Actinomycin-D (VA regimen)'] }, { phase: 'Chemotherapy Stage II', duration: '24 weeks', agents: ['Vincristine', 'Actinomycin-D'] }, { phase: 'Radiation', duration: 'If indicated', agents: ['10.8 Gy flank (Stage III)'] } ], longTermFollowUp: ['Renal function (remaining kidney)', 'Abdominal imaging', 'Blood pressure', 'Cardiac (if doxorubicin)'], fertilityPreservation: ['Generally not needed for VA regimen'], lateEffectsMonitoring: ['Hypertension', 'Renal insufficiency', 'Scoliosis (if radiation)'], psychosocialSupport: ['Body image (nephrectomy scar)', 'Return to activities'], references: ['COG AREN0532', 'SIOP 2001', 'Umbrella SIOP-RTSG 2016'] }, { id: 'ped-osteosarcoma', name: 'Osteosarcoma High-Grade', ageGroup: 'adolescent', cancerType: 'Osteosarcoma', riskStratification: ['Non-metastatic', 'Metastatic', 'Histologic response to neoadjuvant (% necrosis)'], treatmentPhases: [ { phase: 'Neoadjuvant', duration: '10 weeks', agents: ['Methotrexate (12g/m²)', 'Cisplatin', 'Doxorubicin', 'MAP regimen'] }, { phase: 'Surgery', duration: 'Week 11', agents: ['Limb salvage or amputation', 'Histologic response assessment'] }, { phase: 'Adjuvant Good Response', duration: '18 weeks', agents: ['MAP continuation'] }, { phase: 'Adjuvant Poor Response', duration: '18 weeks', agents: ['MAP + Ifosfamide + Etoposide (investigational)'] } ], longTermFollowUp: ['Cardiac echo', 'Hearing', 'Renal function', 'Limb function', 'Chest CT surveillance'], fertilityPreservation: ['Sperm banking (males)', 'Oocyte/ovarian tissue (females)', 'GnRH agonist consideration'], lateEffectsMonitoring: ['Cardiomyopathy', 'Ototoxicity', 'Nephrotoxicity', 'Limb length discrepancy', 'Prosthesis function'], psychosocialSupport: ['Limb rehabilitation', 'Peer support', 'Body image', 'Return to sports'], references: ['EURAMOS-1', 'COG AOST1321', 'INT-0133'] }, { id: 'ped-ewing-localized', name: 'Ewing Sarcoma Localized', ageGroup: 'adolescent', cancerType: 'Ewing Sarcoma', riskStratification: ['Tumor location', 'Tumor volume (<200ml vs ≥200ml)', 'Age', 'LDH'], treatmentPhases: [ { phase: 'Induction', duration: '12 weeks (6 cycles)', agents: ['VDC (Vincristine-Doxorubicin-Cyclophosphamide)', 'IE (Ifosfamide-Etoposide)', 'Alternating'] }, { phase: 'Local Control', duration: 'After 6 cycles', agents: ['Surgery preferred if good margins possible', 'Radiation if unresectable or close margins'] }, { phase: 'Consolidation', duration: '23 weeks', agents: ['VDC/IE continuation'] } ], longTermFollowUp: ['Cardiac function', 'Renal function', 'Gonadal function', 'Lung function', 'Secondary malignancies'], fertilityPreservation: ['High priority - alkylating agents cause infertility', 'Mandatory oncofertility consultation'], lateEffectsMonitoring: ['Cardiomyopathy', 'Secondary leukemia', 'Renal dysfunction', 'Infertility'], psychosocialSupport: ['Limb function', 'Chronic pain', 'Fertility counseling', 'Transition to adult care'], references: ['COG AEWS1031', 'EURO-EWING 99', 'rEECur'] }, { id: 'ped-medulloblastoma-sr', name: 'Medulloblastoma Standard Risk', ageGroup: 'child', cancerType: 'Medulloblastoma', riskStratification: ['Age ≥3', 'Total/near-total resection', 'No metastases', 'WNT or SHH-TP53 wild-type'], treatmentPhases: [ { phase: 'Surgery', duration: 'Upfront', agents: ['Maximal safe resection', 'CSF diversion if needed'] }, { phase: 'Radiation', duration: '6 weeks', agents: ['Craniospinal irradiation 23.4 Gy', 'Boost to posterior fossa 54 Gy'] }, { phase: 'Chemotherapy', duration: '48 weeks', agents: ['Cisplatin', 'Vincristine', 'Cyclophosphamide (or lomustine)'] } ], longTermFollowUp: ['Neurocognitive testing', 'Hearing', 'Endocrine', 'Growth', 'Spine imaging', 'Brain MRI'], fertilityPreservation: ['Important especially with cyclophosphamide', 'Pre-pubertal considerations'], lateEffectsMonitoring: ['Cognitive decline', 'Growth hormone deficiency', 'Thyroid dysfunction', 'Hearing loss', 'Secondary tumors'], psychosocialSupport: ['Educational support', 'Neurocognitive rehabilitation', 'Social skills', 'Family support'], references: ['COG ACNS0331', 'SIOP PNET 5', 'SJMB03'] }, { id: 'ped-rhabdomyosarcoma-low', name: 'Rhabdomyosarcoma Low Risk', ageGroup: 'child', cancerType: 'Rhabdomyosarcoma', riskStratification: ['Embryonal histology', 'Stage 1 or 2', 'Group I or II', 'Favorable site (orbit, head non-PM)'], treatmentPhases: [ { phase: 'Chemotherapy', duration: '22-43 weeks', agents: ['Vincristine', 'Actinomycin-D (VA regimen)', 'Cyclophosphamide (subset)'] }, { phase: 'Local Control', duration: 'Week 12', agents: ['Surgery if complete resection possible', 'Radiation for microscopic residual'] } ], longTermFollowUp: ['Second malignancy screening', 'Cardiac function', 'Gonadal function', 'Site-specific monitoring'], fertilityPreservation: ['Lower priority for VA only', 'Higher priority if cyclophosphamide used'], lateEffectsMonitoring: ['Second malignancy', 'Local effects of radiation', 'Growth at treated site'], psychosocialSupport: ['Site-specific (orbit = vision, GU = bladder/bowel)', 'Body image'], references: ['COG ARST0331', 'COG ARST0531'] }, { id: 'ped-retinoblastoma', name: 'Retinoblastoma', ageGroup: 'infant', cancerType: 'Retinoblastoma', riskStratification: ['Unilateral vs bilateral', 'Intraocular classification (A-E)', 'Extraocular disease', 'Germline RB1 mutation'], treatmentPhases: [ { phase: 'Focal Therapy', duration: 'Ongoing', agents: ['Laser photocoagulation', 'Cryotherapy', 'Brachytherapy'] }, { phase: 'Intra-arterial Chemotherapy', duration: 'Cycles as needed', agents: ['Melphalan', 'Topotecan', 'Carboplatin (IAC)'] }, { phase: 'Intravitreal Chemotherapy', duration: 'If vitreous seeds', agents: ['Melphalan intravitreal'] }, { phase: 'Systemic Chemotherapy', duration: 'If needed', agents: ['Carboplatin', 'Etoposide', 'Vincristine (CEV)'] }, { phase: 'Enucleation', duration: 'If salvage not possible', agents: ['Primary or secondary enucleation'] } ], longTermFollowUp: ['Eye exams', 'MRI brain (trilateral screening)', 'Second malignancy surveillance (germline RB1)', 'Genetic counseling'], fertilityPreservation: ['N/A for focal therapy', 'Consider if systemic chemotherapy'], lateEffectsMonitoring: ['Vision', 'Trilateral retinoblastoma', 'Secondary cancers (osteosarcoma if germline)', 'Facial asymmetry'], psychosocialSupport: ['Vision support services', 'Prosthetic eye fitting', 'Family genetic counseling', 'Sibling screening'], references: ['Children\'s Oncology Group', 'CHLA protocols', 'One Retinoblastoma World'] }, { id: 'ped-aml', name: 'Pediatric AML', ageGroup: 'child', cancerType: 'Acute Myeloid Leukemia', riskStratification: ['Cytogenetics (CBF, KMT2A, monosomy 7)', 'Molecular (FLT3, NPM1, CEBPA)', 'Response (MRD after Induction 1)'], treatmentPhases: [ { phase: 'Induction 1', duration: '4 weeks', agents: ['Cytarabine', 'Daunorubicin', 'Etoposide (ADE)'] }, { phase: 'Induction 2', duration: '4 weeks', agents: ['Cytarabine', 'Mitoxantrone (AM)'] }, { phase: 'Consolidation', duration: '2-3 cycles', agents: ['High-dose cytarabine', 'Gemtuzumab ozogamicin (CD33+)'] }, { phase: 'Transplant', duration: 'If high risk', agents: ['Allogeneic HSCT for high-risk'] } ], longTermFollowUp: ['Cardiac function', 'Growth', 'Endocrine', 'Neurocognitive', 'Second malignancy'], fertilityPreservation: ['High priority - intensive therapy', 'All patients should be counseled'], lateEffectsMonitoring: ['Cardiomyopathy', 'MDS/secondary AML', 'Growth failure', 'Endocrine dysfunction'], psychosocialSupport: ['ICU support', 'Prolonged hospitalization support', 'Transplant preparation'], references: ['COG AAML1831', 'AAML0531', 'MyeChild 01'] }, { id: 'ped-brain-low-grade-glioma', name: 'Pediatric Low-Grade Glioma', ageGroup: 'child', cancerType: 'Low-Grade Glioma', riskStratification: ['Location', 'Extent of resection', 'NF1 association', 'BRAF alteration (fusion vs V600E)'], treatmentPhases: [ { phase: 'Observation', duration: 'If stable', agents: ['Serial imaging for NF1-associated or stable'] }, { phase: 'Surgery', duration: 'If progressive or symptomatic', agents: ['Maximal safe resection'] }, { phase: 'Chemotherapy', duration: '70 weeks', agents: ['Carboplatin-vincristine', 'TPCV (thioguanine, procarbazine, CCNU, vincristine)'] }, { phase: 'Targeted Therapy', duration: 'If refractory', agents: ['Selumetinib (NF1)', 'Dabrafenib-trametinib (BRAF V600E)', 'MEK inhibitors'] } ], longTermFollowUp: ['Ophthalmology', 'Endocrine', 'Neurocognitive', 'Long-term imaging'], fertilityPreservation: ['Low priority for CV alone', 'Consider if alkylating agents needed'], lateEffectsMonitoring: ['Visual pathway function', 'Endocrine (hypothalamic-pituitary)', 'Neurocognitive'], psychosocialSupport: ['Vision support', 'Learning support', 'NF1 comprehensive care'], references: ['COG ACNS1831', 'LOGGIC', 'PLGG consensus'] }, { id: 'ped-hepatoblastoma', name: 'Hepatoblastoma', ageGroup: 'infant', cancerType: 'Hepatoblastoma', riskStratification: ['PRETEXT stage (I-IV)', 'Metastatic status', 'AFP levels', 'Age (infants better)'], treatmentPhases: [ { phase: 'Neoadjuvant', duration: '2-4 cycles', agents: ['Cisplatin', 'Doxorubicin (C5VD)', 'PLADO for very low risk'] }, { phase: 'Surgery', duration: 'After neoadjuvant', agents: ['Hepatectomy', 'Liver transplant if unresectable'] }, { phase: 'Adjuvant', duration: '2 cycles', agents: ['Cisplatin-based'] } ], longTermFollowUp: ['Hearing', 'Cardiac function', 'Liver function', 'AFP monitoring', 'Imaging surveillance'], fertilityPreservation: ['Consider in older children', 'Cisplatin causes gonadotoxicity'], lateEffectsMonitoring: ['Ototoxicity', 'Cardiomyopathy', 'Liver regeneration', 'Renal function'], psychosocialSupport: ['NICU/PICU support', 'Transplant preparation if needed', 'Family support'], references: ['SIOPEL protocols', 'COG AHEP0731', 'PHITT'] }, { id: 'ped-germ-cell', name: 'Pediatric Extracranial Germ Cell Tumors', ageGroup: 'child', cancerType: 'Germ Cell Tumor', riskStratification: ['Site (gonadal vs extragonadal)', 'Stage', 'Tumor markers (AFP, β-hCG)', 'Histology'], treatmentPhases: [ { phase: 'Surgery', duration: 'Primary if resectable', agents: ['Orchiectomy', 'Oophorectomy', 'Resection'] }, { phase: 'Chemotherapy Low Risk', duration: '3 cycles', agents: ['PEB (Cisplatin, Etoposide, Bleomycin)'] }, { phase: 'Chemotherapy Intermediate Risk', duration: '4 cycles', agents: ['Compressed PEB (3 days instead of 5)'] }, { phase: 'Chemotherapy High Risk', duration: '4 cycles', agents: ['BEP', 'Consider HD-CarboPEC if very high risk'] } ], longTermFollowUp: ['Tumor markers', 'Gonadal function', 'Hearing', 'Pulmonary function', 'Fertility'], fertilityPreservation: ['Priority for males - orchiectomy + chemo', 'Sperm banking if post-pubertal', 'Oocyte preservation'], lateEffectsMonitoring: ['Hearing loss', 'Pulmonary fibrosis (bleomycin)', 'Infertility', 'Renal dysfunction', 'Secondary leukemia'], psychosocialSupport: ['Body image (orchiectomy)', 'Fertility concerns', 'Sexuality'], references: ['COG AGCT1531', 'MALIGNE 2014', 'TE22'] }, ]; // ═══════════════════════════════════════════════════════════════════════════════ // SUPPORTIVE CARE PROTOCOLS // ═══════════════════════════════════════════════════════════════════════════════ private supportiveCareProtocols: SupportiveCareProtocol[] = [ // SYMPTOM MANAGEMENT { id: 'support-pain-001', name: 'Cancer Pain Management', category: 'symptom_management', indications: ['Tumor-related pain', 'Treatment-related pain', 'Chronic cancer pain', 'Breakthrough pain'], interventions: ['Pain assessment (0-10)', 'WHO analgesic ladder', 'Around-the-clock dosing', 'Rescue dosing', 'Palliative radiation', 'Nerve blocks', 'Intrathecal pumps'], medications: ['Acetaminophen', 'NSAIDs', 'Tramadol', 'Morphine', 'Oxycodone', 'Hydromorphone', 'Fentanyl', 'Methadone', 'Gabapentin', 'Pregabalin', 'Duloxetine', 'Dexamethasone'], complementaryApproaches: ['Acupuncture', 'Massage', 'Physical therapy', 'TENS', 'Mindfulness', 'Hypnosis', 'Music therapy'], outcomes: ['Pain score <4', 'Functional status maintained', 'Minimal sedation', 'Quality of life improvement'], references: ['NCCN Cancer Pain', 'WHO Guidelines', 'ASCO Pain Guidelines'] }, { id: 'support-nausea-001', name: 'Chemotherapy-Induced Nausea/Vomiting', category: 'symptom_management', indications: ['Highly emetogenic chemotherapy', 'Moderately emetogenic chemotherapy', 'Anticipatory nausea', 'Breakthrough nausea'], interventions: ['Risk assessment', 'Prophylactic antiemetics', 'Rescue antiemetics', 'Delayed emesis prevention'], medications: ['Ondansetron', 'Granisetron', 'Palonosetron', 'Dexamethasone', 'Aprepitant', 'Fosaprepitant', 'Netupitant-palonosetron', 'Rolapitant', 'Olanzapine', 'Lorazepam', 'Prochlorperazine'], complementaryApproaches: ['Ginger', 'Acupuncture', 'Acupressure (P6)', 'Behavioral therapy', 'Progressive muscle relaxation'], outcomes: ['Complete response (no vomiting, no rescue)', 'Minimal nausea impact on function'], references: ['NCCN Antiemesis', 'ASCO/MASCC Guidelines'] }, { id: 'support-fatigue-001', name: 'Cancer-Related Fatigue', category: 'symptom_management', indications: ['Treatment-related fatigue', 'Cancer-related fatigue', 'Persistent post-treatment fatigue'], interventions: ['Fatigue screening', 'Treatable cause evaluation (anemia, thyroid, depression)', 'Energy conservation', 'Exercise prescription', 'Sleep hygiene', 'Cognitive behavioral therapy'], medications: ['Methylphenidate', 'Modafinil', 'American ginseng', 'Dexamethasone (short-term)'], complementaryApproaches: ['Aerobic exercise', 'Resistance training', 'Yoga', 'Tai chi', 'Mindfulness-based stress reduction'], outcomes: ['Reduced fatigue scores', 'Improved function', 'Maintained activity levels'], references: ['NCCN Fatigue', 'ASCO Fatigue Guidelines'] }, { id: 'support-anorexia-001', name: 'Cancer Anorexia-Cachexia', category: 'nutritional', indications: ['Weight loss >5% in 6 months', 'Reduced oral intake', 'Muscle wasting', 'Elevated CRP'], interventions: ['Nutritional assessment', 'Dietary counseling', 'Oral nutritional supplements', 'Appetite stimulants', 'Enteral nutrition', 'Parenteral nutrition (select cases)'], medications: ['Megestrol acetate', 'Dronabinol', 'Corticosteroids (short-term)', 'Olanzapine', 'Mirtazapine'], complementaryApproaches: ['Small frequent meals', 'Ginger for nausea', 'Exercise to maintain muscle'], outcomes: ['Weight stabilization', 'Improved appetite', 'Maintained function'], references: ['ESPEN Cancer Nutrition', 'ASPEN Guidelines'] }, { id: 'support-diarrhea-001', name: 'Treatment-Related Diarrhea', category: 'symptom_management', indications: ['Chemotherapy-induced diarrhea', 'Targeted therapy diarrhea', 'Radiation enteritis', 'Immunotherapy colitis'], interventions: ['Grading assessment', 'Infectious workup', 'Diet modification', 'Hydration', 'Medication management'], medications: ['Loperamide', 'Diphenoxylate-atropine', 'Octreotide', 'Tincture of opium', 'Budesonide (immunotherapy)', 'Prednisone (immunotherapy colitis)'], complementaryApproaches: ['BRAT diet', 'Probiotics (with caution)', 'Soluble fiber', 'Adequate hydration'], outcomes: ['Grade reduction', 'Prevention of dehydration', 'Maintained treatment'], references: ['NCCN Management', 'ASCO Diarrhea Guidelines'] }, { id: 'support-neuropathy-001', name: 'Chemotherapy-Induced Peripheral Neuropathy', category: 'symptom_management', indications: ['Platinum-induced', 'Taxane-induced', 'Vinca alkaloid-induced', 'Bortezomib-induced'], interventions: ['Risk assessment', 'Dose modification', 'Symptom management', 'Physical therapy', 'Occupational therapy'], medications: ['Duloxetine', 'Gabapentin', 'Pregabalin', 'Lidocaine patches', 'Capsaicin cream', 'Tricyclic antidepressants'], complementaryApproaches: ['Acupuncture', 'Exercise', 'Balance training', 'Cryotherapy (prevention)'], outcomes: ['Maintained function', 'Pain control', 'Continued treatment when possible'], references: ['ASCO CIPN Guidelines', 'NCCN Survivorship'] }, { id: 'support-mucositis-001', name: 'Oral Mucositis', category: 'symptom_management', indications: ['Chemotherapy-induced', 'Radiation-induced (head/neck)', 'Post-transplant'], interventions: ['Oral care protocol', 'Pain management', 'Nutritional support', 'Infection prevention'], medications: ['Palifermin (HSCT)', 'Magic mouthwash', 'Lidocaine viscous', 'Morphine (severe)', 'Benzydamine', 'Dexamethasone rinse'], complementaryApproaches: ['Saline rinses', 'Sodium bicarbonate rinses', 'Ice chips (cryotherapy)', 'Honey'], outcomes: ['Grade reduction', 'Pain control', 'Maintained nutrition', 'Prevented secondary infection'], references: ['MASCC/ISOO Guidelines', 'NCCN Mucositis'] }, { id: 'support-skin-001', name: 'Dermatologic Toxicity Management', category: 'symptom_management', indications: ['EGFR inhibitor rash', 'Hand-foot syndrome', 'Radiation dermatitis', 'Immunotherapy skin toxicity'], interventions: ['Skin assessment', 'Prophylaxis (where indicated)', 'Topical management', 'Systemic therapy if severe'], medications: ['Hydrocortisone cream', 'Clindamycin gel', 'Doxycycline (prophylactic for EGFR)', 'Urea cream', 'Moisturizers', 'Prednisone (immune-related)'], complementaryApproaches: ['Sun protection', 'Gentle skin care', 'Loose-fitting clothes', 'Radiation skin care protocols'], outcomes: ['Maintained treatment', 'Grade reduction', 'Quality of life preservation'], references: ['NCCN Supportive Care', 'MASCC Skin Toxicity'] }, // PSYCHOSOCIAL SUPPORT { id: 'support-distress-001', name: 'Psychosocial Distress Screening', category: 'psychosocial', indications: ['All cancer patients', 'Distress thermometer ≥4', 'Major life transitions', 'Treatment changes'], interventions: ['Distress screening', 'Psychological assessment', 'Social work referral', 'Psychiatry referral', 'Support groups', 'Counseling'], medications: ['SSRIs', 'SNRIs', 'Benzodiazepines (short-term)', 'Sleep aids'], complementaryApproaches: ['Mindfulness-based stress reduction', 'Cognitive behavioral therapy', 'Meaning-centered psychotherapy', 'Art/music therapy', 'Peer support'], outcomes: ['Reduced distress scores', 'Improved coping', 'Better treatment adherence'], references: ['NCCN Distress', 'ASCO Anxiety/Depression', 'IPOS Standards'] }, { id: 'support-depression-001', name: 'Cancer-Related Depression', category: 'psychosocial', indications: ['PHQ-9 ≥10', 'Major depressive episode', 'Adjustment disorder with depressed mood'], interventions: ['Psychiatric evaluation', 'Psychotherapy', 'Medication management', 'Suicide risk assessment'], medications: ['Sertraline', 'Escitalopram', 'Mirtazapine (with appetite/sleep benefits)', 'Bupropion (low fatigue)', 'Methylphenidate (prognosis limited)'], complementaryApproaches: ['CBT', 'Problem-solving therapy', 'Behavioral activation', 'Exercise', 'Light therapy'], outcomes: ['PHQ-9 response (≥50% reduction)', 'Improved function', 'Quality of life improvement'], references: ['NCCN Distress', 'ASCO Depression'] }, { id: 'support-delirium-001', name: 'Cancer-Related Delirium', category: 'psychosocial', indications: ['Acute confusion', 'ICU patients', 'Opioid toxicity', 'Metabolic derangement', 'Brain metastases'], interventions: ['Reversible cause evaluation', 'Non-pharmacologic management', 'Safety measures', 'Family education'], medications: ['Haloperidol', 'Quetiapine', 'Olanzapine', 'Avoid benzodiazepines (except alcohol withdrawal)'], complementaryApproaches: ['Reorientation', 'Sleep-wake cycle preservation', 'Mobility', 'Sensory aids (glasses, hearing aids)', 'Family presence'], outcomes: ['Resolution of delirium', 'Prevention of harm', 'Family comfort'], references: ['NCCN Palliative Care', 'ASCO Delirium'] }, // REHABILITATION { id: 'support-rehab-001', name: 'Cancer Rehabilitation', category: 'rehabilitation', indications: ['Physical deconditioning', 'Post-surgical recovery', 'Lymphedema', 'Cognitive impairment', 'Speech/swallowing issues'], interventions: ['Physiatry consultation', 'Physical therapy', 'Occupational therapy', 'Speech therapy', 'Lymphedema management', 'Cognitive rehabilitation'], medications: ['Pain management', 'Spasticity management'], complementaryApproaches: ['Exercise programs', 'Aquatic therapy', 'Yoga', 'Pilates', 'Pelvic floor therapy'], outcomes: ['Improved function', 'Return to activities', 'Quality of life', 'Independence'], references: ['NCCN Survivorship', 'ACRM Cancer Rehab'] }, // SURVIVORSHIP { id: 'support-survivorship-001', name: 'Cancer Survivorship Care', category: 'survivorship', indications: ['Completion of active treatment', 'Long-term survivors', 'Transition to survivorship'], interventions: ['Survivorship care plan', 'Surveillance schedule', 'Late effects monitoring', 'Health promotion', 'Care coordination'], medications: ['Depending on late effects'], complementaryApproaches: ['Exercise', 'Nutrition counseling', 'Smoking cessation', 'Stress management'], outcomes: ['Early recurrence detection', 'Late effect management', 'Healthy lifestyle', 'Quality of life'], references: ['NCCN Survivorship', 'ASCO Survivorship Guidelines'] }, { id: 'support-sexual-health-001', name: 'Cancer-Related Sexual Health', category: 'survivorship', indications: ['Sexual dysfunction', 'Hormonal changes', 'Body image issues', 'Fertility concerns'], interventions: ['Sexual health screening', 'Counseling', 'Hormone management', 'Pelvic floor therapy', 'Prosthetics/aids'], medications: ['Vaginal estrogens', 'Lubricants', 'PDE5 inhibitors', 'Testosterone (men)', 'Ospemifene'], complementaryApproaches: ['Couples counseling', 'Sex therapy', 'Body image work', 'Mindfulness'], outcomes: ['Improved sexual function', 'Relationship satisfaction', 'Quality of life'], references: ['NCCN Survivorship', 'ASCO Sexual Health'] }, // PALLIATIVE CARE { id: 'support-palliative-integration', name: 'Early Palliative Care Integration', category: 'palliative', indications: ['Advanced cancer diagnosis', 'High symptom burden', 'Goals of care discussion needed', 'Complex decision-making'], interventions: ['Palliative care consultation', 'Symptom management', 'Goals of care discussion', 'Advance care planning', 'Family meetings', 'Care coordination'], medications: ['Symptom-directed medications'], complementaryApproaches: ['Spiritual care', 'Music therapy', 'Art therapy', 'Legacy work', 'Dignity therapy'], outcomes: ['Improved quality of life', 'Better symptom control', 'Goal-concordant care', 'Reduced aggressive end-of-life care'], references: ['ASCO Palliative Care', 'NCCN Palliative Care', 'Temel NEJM'] }, { id: 'support-hospice-001', name: 'Hospice Care', category: 'end_of_life', indications: ['Prognosis ≤6 months', 'Goals focused on comfort', 'Decision to forego curative treatment'], interventions: ['Hospice enrollment', 'Home-based care', 'Inpatient hospice if needed', 'Respite care', 'Bereavement support'], medications: ['Comfort medications', 'Symptom management'], complementaryApproaches: ['Spiritual care', 'Life review', 'Family support', 'Bereavement counseling'], outcomes: ['Comfortable death', 'Family support', 'Goal-concordant care', 'Bereavement support'], references: ['NHPCO Guidelines', 'NCCN Palliative Care'] }, { id: 'support-dyspnea-001', name: 'Cancer-Related Dyspnea', category: 'palliative', indications: ['Malignant pleural effusion', 'Lymphangitic carcinomatosis', 'Airway obstruction', 'End-of-life dyspnea'], interventions: ['Cause-directed treatment', 'Thoracentesis/pleurodesis', 'Symptom management', 'Oxygen (if hypoxic)', 'Fan therapy'], medications: ['Morphine (low-dose)', 'Hydromorphone', 'Benzodiazepines (anxiety component)', 'Corticosteroids'], complementaryApproaches: ['Positioning', 'Breathing exercises', 'Relaxation techniques', 'Fan across face', 'Energy conservation'], outcomes: ['Reduced dyspnea scores', 'Improved function', 'Quality of life'], references: ['NCCN Palliative Care', 'Cochrane Reviews'] }, ]; // ═══════════════════════════════════════════════════════════════════════════════ // PUBLIC API METHODS // ═══════════════════════════════════════════════════════════════════════════════ async getGlobalGuidelines(region?: string, country?: string, cancerType?: string): Promise { let guidelines = [ ...this.asianGuidelines, ...this.africanGuidelines, ...this.latinAmericanGuidelines, ...this.middleEasternGuidelines, ...this.whoGuidelines ]; if (region) { guidelines = guidelines.filter(g => g.region === region); } if (country) { guidelines = guidelines.filter(g => g.country === country); } if (cancerType) { guidelines = guidelines.filter(g => g.cancerType.toLowerCase().includes(cancerType.toLowerCase()) ); } return guidelines; } async getSpecialPopulationProtocol(population: string, cancerType?: string): Promise { let protocols = this.specialPopulationProtocols; if (population) { protocols = protocols.filter(p => p.population === population); } if (cancerType) { protocols = protocols.filter(p => p.cancerType.toLowerCase().includes(cancerType.toLowerCase()) ); } return protocols; } async getResourceLimitedAdaptation(setting: string, originalProtocol?: string): Promise { let adaptations = this.resourceLimitedAdaptations; if (setting) { adaptations = adaptations.filter(a => a.setting === setting); } if (originalProtocol) { adaptations = adaptations.filter(a => a.originalProtocol.toLowerCase().includes(originalProtocol.toLowerCase()) ); } return adaptations; } async getRareCancerProtocol(cancerName: string): Promise { return this.rareCancerProtocols.find(p => p.name.toLowerCase().includes(cancerName.toLowerCase()) ); } async getAllRareCancerProtocols(): Promise { return this.rareCancerProtocols; } async getPediatricProtocol(cancerType: string, ageGroup?: string): Promise { let protocols = this.pediatricProtocols; if (cancerType) { protocols = protocols.filter(p => p.cancerType.toLowerCase().includes(cancerType.toLowerCase()) || p.name.toLowerCase().includes(cancerType.toLowerCase()) ); } if (ageGroup) { protocols = protocols.filter(p => p.ageGroup === ageGroup); } return protocols; } async getAllPediatricProtocols(): Promise { return this.pediatricProtocols; } async getSupportiveCareProtocol(category: string): Promise { return this.supportiveCareProtocols.filter(p => p.category === category); } async getAllSupportiveCareProtocols(): Promise { return this.supportiveCareProtocols; } // ═══════════════════════════════════════════════════════════════════════════════ // COMPREHENSIVE TREATMENT RECOMMENDATION ENGINE // ═══════════════════════════════════════════════════════════════════════════════ async getComprehensiveTreatmentPlan( cancerType: string, stage: string, patientCharacteristics: { age: number; region: string; resourceSetting: 'high_income' | 'middle_income' | 'low_income'; specialPopulation?: 'pediatric' | 'adolescent_young_adult' | 'elderly' | 'pregnant' | 'immunocompromised'; comorbidities?: string[]; } ): Promise<{ primaryProtocol: GlobalTreatmentGuideline | null; specialPopulationModifications: SpecialPopulationProtocol | null; resourceAdaptations: ResourceLimitedAdaptation | null; supportiveCareNeeds: SupportiveCareProtocol[]; pediatricProtocol: PediatricOncologyProtocol | null; rareCancerConsiderations: RareCancerProtocol | null; recommendations: string[]; }> { const recommendations: string[] = []; // Get primary regional guideline const regionalGuidelines = await this.getGlobalGuidelines(undefined, undefined, cancerType); let primaryProtocol = regionalGuidelines.find(g => g.region === patientCharacteristics.region || g.region === 'Global' || g.region === 'WHO' ) || null; if (primaryProtocol) { recommendations.push(`📋 Primary guideline: ${primaryProtocol.name} (${primaryProtocol.organization})`); } // Get special population modifications let specialPopulationMods: SpecialPopulationProtocol | null = null; if (patientCharacteristics.specialPopulation) { const mods = await this.getSpecialPopulationProtocol( patientCharacteristics.specialPopulation, cancerType ); specialPopulationMods = mods[0] || null; if (specialPopulationMods) { recommendations.push(`👥 Special population: ${specialPopulationMods.name}`); recommendations.push(...specialPopulationMods.modifications.slice(0, 3).map(m => ` • ${m}`)); } } // Get resource adaptations if needed let resourceAdaptations: ResourceLimitedAdaptation | null = null; if (patientCharacteristics.resourceSetting !== 'high_income') { const adaptations = await this.getResourceLimitedAdaptation( patientCharacteristics.resourceSetting ); resourceAdaptations = adaptations[0] || null; if (resourceAdaptations) { recommendations.push(`💰 Resource adaptation available: ${resourceAdaptations.originalProtocol}`); } } // Get pediatric protocol if applicable let pediatricProtocol: PediatricOncologyProtocol | null = null; if (patientCharacteristics.age < 18) { const peds = await this.getPediatricProtocol(cancerType); pediatricProtocol = peds[0] || null; if (pediatricProtocol) { recommendations.push(`🧒 Pediatric protocol: ${pediatricProtocol.name}`); } } // Check for rare cancer const rareCancer = await this.getRareCancerProtocol(cancerType); if (rareCancer) { recommendations.push(`🔬 Rare cancer consideration: ${rareCancer.name}`); recommendations.push(` Referral centers: ${rareCancer.referralCenters.slice(0, 2).join(', ')}`); } // Get supportive care needs const allSupportive = await this.getAllSupportiveCareProtocols(); const supportiveNeeds = allSupportive.filter(s => s.category === 'symptom_management' || s.category === 'psychosocial' ).slice(0, 5); recommendations.push(`🏥 Supportive care considerations:`); supportiveNeeds.forEach(s => { recommendations.push(` • ${s.name}`); }); return { primaryProtocol, specialPopulationModifications: specialPopulationMods, resourceAdaptations, supportiveCareNeeds: supportiveNeeds, pediatricProtocol, rareCancerConsiderations: rareCancer || null, recommendations }; } // ═══════════════════════════════════════════════════════════════════════════════ // STATISTICS AND COVERAGE METRICS // ═══════════════════════════════════════════════════════════════════════════════ getCoverageStatistics(): { totalGlobalGuidelines: number; regionsRepresented: string[]; totalRareCancers: number; totalPediatricProtocols: number; totalSupportiveCareProtocols: number; totalSpecialPopulations: number; resourceSettings: string[]; } { const allGuidelines = [ ...this.asianGuidelines, ...this.africanGuidelines, ...this.latinAmericanGuidelines, ...this.middleEasternGuidelines, ...this.whoGuidelines ]; const regions = [...new Set(allGuidelines.map(g => g.region))]; const resourceSettings = [...new Set(this.resourceLimitedAdaptations.map(r => r.setting))]; return { totalGlobalGuidelines: allGuidelines.length, regionsRepresented: regions, totalRareCancers: this.rareCancerProtocols.length, totalPediatricProtocols: this.pediatricProtocols.length, totalSupportiveCareProtocols: this.supportiveCareProtocols.length, totalSpecialPopulations: this.specialPopulationProtocols.length, resourceSettings }; } }