@erosolaraijs/cure 2.0.0 → 2.1.0

package/src/capabilities/cancerTreatmentCapability.ts

@@ -631,7 +631,213 @@ export class CancerTreatmentCapabilityModule {
       cancerTypes: ['Pancreatic', 'Glioblastoma', 'NSCLC', 'Mesothelioma'],
       approvedDrugs: ['MAT2A inhibitors (investigational)', 'PRMT5 inhibitors (investigational)'],
       mechanismOfAction: 'Synthetic lethality in MTAP-deleted tumors',
-      evidenceLevel: 'Phase II', biomarker: 'MTAP deletion (co-deleted with CDKN2A)' }
+      evidenceLevel: 'Phase II', biomarker: 'MTAP deletion (co-deleted with CDKN2A)' },
+
+    // === ALL KRAS VARIANTS ===
+    { gene: 'KRAS G12D', protein: 'KRAS G12D Mutant', pathway: 'RAS/MAPK',
+      cancerTypes: ['Pancreatic', 'Colorectal', 'NSCLC', 'Endometrial'],
+      approvedDrugs: ['MRTX1133 (investigational)', 'RMC-9805 (investigational)'],
+      mechanismOfAction: 'Direct KRAS G12D inhibition',
+      evidenceLevel: 'Phase I', biomarker: 'KRAS G12D mutation' },
+    { gene: 'KRAS G12V', protein: 'KRAS G12V Mutant', pathway: 'RAS/MAPK',
+      cancerTypes: ['Pancreatic', 'Colorectal', 'NSCLC'],
+      approvedDrugs: ['Pan-RAS inhibitors (investigational)', 'SOS1 inhibitors'],
+      mechanismOfAction: 'Indirect KRAS inhibition strategies',
+      evidenceLevel: 'Phase I', biomarker: 'KRAS G12V mutation' },
+    { gene: 'KRAS G13D', protein: 'KRAS G13D Mutant', pathway: 'RAS/MAPK',
+      cancerTypes: ['Colorectal', 'NSCLC'],
+      approvedDrugs: ['Cetuximab (may respond)', 'SHP2 inhibitors'],
+      mechanismOfAction: 'EGFR antibodies may work in G13D',
+      evidenceLevel: 'Phase II', biomarker: 'KRAS G13D mutation' },
+    { gene: 'KRAS G12R', protein: 'KRAS G12R Mutant', pathway: 'RAS/MAPK',
+      cancerTypes: ['Pancreatic'],
+      approvedDrugs: ['Pan-RAS inhibitors (investigational)'],
+      mechanismOfAction: 'Novel RAS inhibition approaches',
+      evidenceLevel: 'Phase I', biomarker: 'KRAS G12R mutation' },
+    { gene: 'KRAS Q61H/L/K', protein: 'KRAS Q61 Mutants', pathway: 'RAS/MAPK',
+      cancerTypes: ['Melanoma', 'NSCLC', 'Colorectal'],
+      approvedDrugs: ['MEK inhibitors', 'ERK inhibitors (investigational)'],
+      mechanismOfAction: 'Downstream pathway inhibition',
+      evidenceLevel: 'Phase II', biomarker: 'KRAS Q61 mutations' },
+    { gene: 'NRAS Q61', protein: 'NRAS Q61 Mutant', pathway: 'RAS/MAPK',
+      cancerTypes: ['Melanoma', 'AML', 'Colorectal'],
+      approvedDrugs: ['Binimetinib', 'MEK inhibitors'],
+      mechanismOfAction: 'MEK inhibition for NRAS-mutant tumors',
+      evidenceLevel: 'FDA-Approved', biomarker: 'NRAS mutation' },
+    { gene: 'HRAS', protein: 'HRAS Mutant', pathway: 'RAS/MAPK',
+      cancerTypes: ['Head and Neck', 'Bladder', 'Thyroid'],
+      approvedDrugs: ['Tipifarnib'],
+      mechanismOfAction: 'Farnesyltransferase inhibition',
+      evidenceLevel: 'FDA-Approved', biomarker: 'HRAS mutation' },
+
+    // === HEREDITARY CANCER SYNDROME TARGETS ===
+    { gene: 'MLH1/MSH2/MSH6/PMS2', protein: 'Mismatch Repair Proteins', pathway: 'DNA Repair',
+      cancerTypes: ['Lynch Syndrome Cancers', 'Colorectal', 'Endometrial', 'Ovarian', 'Gastric'],
+      approvedDrugs: ['Pembrolizumab', 'Nivolumab', 'Dostarlimab'],
+      mechanismOfAction: 'Immunotherapy for dMMR tumors',
+      evidenceLevel: 'FDA-Approved', biomarker: 'dMMR/MSI-H (Lynch syndrome)' },
+    { gene: 'TP53 (Li-Fraumeni)', protein: 'p53 Tumor Suppressor', pathway: 'Cell Cycle/Apoptosis',
+      cancerTypes: ['Li-Fraumeni Syndrome', 'Sarcoma', 'Breast', 'Brain', 'Adrenocortical'],
+      approvedDrugs: ['Intensive surveillance', 'MDM2 inhibitors (investigational)', 'Gene therapy (investigational)'],
+      mechanismOfAction: 'Restore p53 function or surveillance',
+      evidenceLevel: 'Phase II', biomarker: 'Germline TP53 mutation' },
+    { gene: 'APC', protein: 'Adenomatous Polyposis Coli', pathway: 'Wnt/β-catenin',
+      cancerTypes: ['FAP Colorectal', 'Desmoid Tumor'],
+      approvedDrugs: ['Sulindac', 'Celecoxib', 'Nirogacestat (desmoid)'],
+      mechanismOfAction: 'COX inhibition, Notch inhibition',
+      evidenceLevel: 'FDA-Approved', biomarker: 'APC mutation (FAP)' },
+    { gene: 'STK11/LKB1', protein: 'Serine/Threonine Kinase 11', pathway: 'AMPK/mTOR',
+      cancerTypes: ['Peutz-Jeghers Syndrome', 'NSCLC', 'Cervical'],
+      approvedDrugs: ['mTOR inhibitors', 'Chemotherapy (reduced ICI response)'],
+      mechanismOfAction: 'Target downstream pathways',
+      evidenceLevel: 'Phase II', biomarker: 'STK11/LKB1 loss' },
+    { gene: 'PTEN (Cowden)', protein: 'PTEN Tumor Suppressor', pathway: 'PI3K/AKT',
+      cancerTypes: ['Cowden Syndrome', 'Breast', 'Thyroid', 'Endometrial'],
+      approvedDrugs: ['PI3K inhibitors', 'AKT inhibitors', 'mTOR inhibitors'],
+      mechanismOfAction: 'Inhibit hyperactive PI3K pathway',
+      evidenceLevel: 'FDA-Approved', biomarker: 'PTEN loss (Cowden syndrome)' },
+    { gene: 'CDH1', protein: 'E-cadherin', pathway: 'Cell Adhesion',
+      cancerTypes: ['Hereditary Diffuse Gastric Cancer', 'Lobular Breast'],
+      approvedDrugs: ['Prophylactic gastrectomy', 'Surveillance', 'Standard chemo'],
+      mechanismOfAction: 'Surgical prevention or standard treatment',
+      evidenceLevel: 'FDA-Approved', biomarker: 'CDH1 germline mutation' },
+    { gene: 'CHEK2', protein: 'Checkpoint Kinase 2', pathway: 'DNA Damage Response',
+      cancerTypes: ['Breast', 'Colorectal', 'Prostate'],
+      approvedDrugs: ['PARP inhibitors (investigational)', 'ATR inhibitors'],
+      mechanismOfAction: 'Exploit DNA repair deficiency',
+      evidenceLevel: 'Phase II', biomarker: 'CHEK2 mutation' },
+    { gene: 'PALB2', protein: 'Partner and Localizer of BRCA2', pathway: 'Homologous Recombination',
+      cancerTypes: ['Breast', 'Pancreatic', 'Ovarian'],
+      approvedDrugs: ['Olaparib', 'Rucaparib', 'Platinum chemotherapy'],
+      mechanismOfAction: 'PARP inhibition for HRD',
+      evidenceLevel: 'FDA-Approved', biomarker: 'PALB2 mutation' },
+    { gene: 'RAD51C/D', protein: 'RAD51 Paralogs', pathway: 'Homologous Recombination',
+      cancerTypes: ['Ovarian', 'Breast'],
+      approvedDrugs: ['PARP inhibitors', 'Platinum'],
+      mechanismOfAction: 'Synthetic lethality in HRD',
+      evidenceLevel: 'FDA-Approved', biomarker: 'RAD51C/D mutation' },
+    { gene: 'BAP1', protein: 'BRCA1-Associated Protein 1', pathway: 'Chromatin/DNA Repair',
+      cancerTypes: ['Mesothelioma', 'Uveal Melanoma', 'RCC', 'Cholangiocarcinoma'],
+      approvedDrugs: ['EZH2 inhibitors (investigational)', 'PARP inhibitors', 'Immunotherapy'],
+      mechanismOfAction: 'Exploit epigenetic vulnerability',
+      evidenceLevel: 'Phase II', biomarker: 'BAP1 loss/mutation' },
+    { gene: 'MEN1', protein: 'Menin', pathway: 'Transcription Regulation',
+      cancerTypes: ['MEN1 Syndrome', 'Pancreatic NET', 'Pituitary', 'Parathyroid'],
+      approvedDrugs: ['Somatostatin analogues', 'Everolimus', 'Sunitinib'],
+      mechanismOfAction: 'Manage neuroendocrine tumors',
+      evidenceLevel: 'FDA-Approved', biomarker: 'MEN1 germline mutation' },
+    { gene: 'RB1', protein: 'Retinoblastoma Protein', pathway: 'Cell Cycle',
+      cancerTypes: ['Retinoblastoma', 'Osteosarcoma', 'SCLC'],
+      approvedDrugs: ['CDK4/6 inhibitors (if RB intact)', 'Chemotherapy', 'Focal therapy'],
+      mechanismOfAction: 'Target cell cycle or standard therapy',
+      evidenceLevel: 'FDA-Approved', biomarker: 'RB1 mutation/loss' },
+
+    // === HIV/IMMUNOCOMPROMISED CANCER TARGETS ===
+    { gene: 'HHV8/KSHV', protein: 'Kaposi Sarcoma Herpesvirus', pathway: 'Viral Oncogenesis',
+      cancerTypes: ['Kaposi Sarcoma', 'Primary Effusion Lymphoma', 'Multicentric Castleman'],
+      approvedDrugs: ['ART', 'Liposomal Doxorubicin', 'Paclitaxel', 'Pomalidomide', 'Siltuximab'],
+      mechanismOfAction: 'Immune reconstitution + direct therapy',
+      evidenceLevel: 'FDA-Approved', biomarker: 'HHV8+ malignancy' },
+    { gene: 'EBV', protein: 'Epstein-Barr Virus', pathway: 'Viral Oncogenesis',
+      cancerTypes: ['PTLD', 'Nasopharyngeal', 'Burkitt Lymphoma', 'Hodgkin', 'Gastric'],
+      approvedDrugs: ['Rituximab (PTLD)', 'EBV-specific CTLs', 'Tabelecleucel', 'Chemotherapy'],
+      mechanismOfAction: 'Target EBV+ cells or reduce immunosuppression',
+      evidenceLevel: 'FDA-Approved', biomarker: 'EBV+ malignancy' },
+    { gene: 'HPV', protein: 'Human Papillomavirus', pathway: 'Viral Oncogenesis',
+      cancerTypes: ['Cervical', 'OPSCC', 'Anal', 'Vulvar', 'Vaginal', 'Penile'],
+      approvedDrugs: ['Tisotumab Vedotin', 'Pembrolizumab', 'Chemoradiation'],
+      mechanismOfAction: 'Target HPV-driven cancers',
+      evidenceLevel: 'FDA-Approved', biomarker: 'HPV+ cancer' },
+    { gene: 'HBV/HCV', protein: 'Hepatitis B/C Viruses', pathway: 'Viral Oncogenesis',
+      cancerTypes: ['HCC'],
+      approvedDrugs: ['Antiviral therapy', 'Atezolizumab-Bevacizumab', 'Sorafenib', 'Lenvatinib'],
+      mechanismOfAction: 'Viral suppression + HCC treatment',
+      evidenceLevel: 'FDA-Approved', biomarker: 'HBV/HCV-related HCC' },
+
+    // === CNS-PENETRANT THERAPY TARGETS ===
+    { gene: 'CNS-EGFR', protein: 'CNS-Penetrant EGFR Inhibition', pathway: 'EGFR',
+      cancerTypes: ['NSCLC Brain Mets', 'EGFR+ with LMD'],
+      approvedDrugs: ['Osimertinib (CNS-penetrant)', 'High-dose Gefitinib'],
+      mechanismOfAction: 'Cross blood-brain barrier',
+      evidenceLevel: 'FDA-Approved', biomarker: 'EGFR+ NSCLC with CNS disease' },
+    { gene: 'CNS-ALK', protein: 'CNS-Penetrant ALK Inhibition', pathway: 'ALK',
+      cancerTypes: ['ALK+ NSCLC Brain Mets'],
+      approvedDrugs: ['Lorlatinib', 'Alectinib', 'Brigatinib'],
+      mechanismOfAction: 'High CNS penetration',
+      evidenceLevel: 'FDA-Approved', biomarker: 'ALK+ NSCLC with CNS disease' },
+    { gene: 'CNS-HER2', protein: 'CNS-Penetrant HER2 Therapy', pathway: 'HER2',
+      cancerTypes: ['HER2+ Breast Brain Mets'],
+      approvedDrugs: ['Tucatinib + Trastuzumab', 'T-DXd', 'Lapatinib'],
+      mechanismOfAction: 'CNS-penetrant HER2 inhibition',
+      evidenceLevel: 'FDA-Approved', biomarker: 'HER2+ breast with CNS disease' },
+    { gene: 'CNS-Melanoma', protein: 'CNS-Active Melanoma Therapy', pathway: 'Multiple',
+      cancerTypes: ['Melanoma Brain Mets'],
+      approvedDrugs: ['Nivolumab + Ipilimumab', 'BRAF/MEK (if BRAF+)', 'SRS'],
+      mechanismOfAction: 'Immunotherapy reaches CNS',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Melanoma with CNS disease' },
+
+    // === RESISTANCE MECHANISM TARGETS ===
+    { gene: 'EGFR C797S', protein: 'EGFR C797S Resistance', pathway: 'EGFR',
+      cancerTypes: ['NSCLC post-Osimertinib'],
+      approvedDrugs: ['Amivantamab', 'Chemotherapy', 'EGFR-MET bispecifics', '4th-gen TKIs (investigational)'],
+      mechanismOfAction: 'Overcome covalent TKI resistance',
+      evidenceLevel: 'FDA-Approved', biomarker: 'EGFR C797S after osimertinib' },
+    { gene: 'ALK Resistance', protein: 'ALK Compound Mutations', pathway: 'ALK',
+      cancerTypes: ['ALK+ NSCLC resistant'],
+      approvedDrugs: ['Lorlatinib', 'Sequential ALK TKIs based on mutation'],
+      mechanismOfAction: 'Select TKI by resistance profile',
+      evidenceLevel: 'FDA-Approved', biomarker: 'ALK resistance mutations' },
+    { gene: 'ESR1 Mutations', protein: 'Estrogen Receptor Mutations', pathway: 'Hormone',
+      cancerTypes: ['HR+ Breast post-AI'],
+      approvedDrugs: ['Elacestrant', 'Fulvestrant', 'Novel SERDs'],
+      mechanismOfAction: 'SERD for ESR1-mutant breast cancer',
+      evidenceLevel: 'FDA-Approved', biomarker: 'ESR1 mutation' },
+    { gene: 'AR Splice Variants', protein: 'AR-V7', pathway: 'Hormone',
+      cancerTypes: ['mCRPC'],
+      approvedDrugs: ['Taxanes preferred', 'PSMA radioligand', 'Consider avoiding AR-targeted'],
+      mechanismOfAction: 'AR-V7+ predicts AR therapy resistance',
+      evidenceLevel: 'FDA-Approved', biomarker: 'AR-V7 positive' },
+    { gene: 'BTK C481S', protein: 'BTK Covalent Resistance', pathway: 'BCR Signaling',
+      cancerTypes: ['CLL/MCL post-Ibrutinib'],
+      approvedDrugs: ['Pirtobrutinib', 'Venetoclax', 'Non-covalent BTK inhibitors'],
+      mechanismOfAction: 'Non-covalent BTK inhibition',
+      evidenceLevel: 'FDA-Approved', biomarker: 'BTK C481S mutation' },
+    { gene: 'BCR-ABL T315I', protein: 'BCR-ABL Gatekeeper Mutation', pathway: 'BCR-ABL',
+      cancerTypes: ['CML', 'Ph+ ALL'],
+      approvedDrugs: ['Ponatinib', 'Asciminib'],
+      mechanismOfAction: 'Overcome T315I resistance',
+      evidenceLevel: 'FDA-Approved', biomarker: 'BCR-ABL T315I' },
+    { gene: 'MET Amplification', protein: 'MET Bypass Resistance', pathway: 'MET',
+      cancerTypes: ['EGFR+ NSCLC resistant'],
+      approvedDrugs: ['Amivantamab + Lazertinib', 'Capmatinib + Osimertinib', 'Tepotinib'],
+      mechanismOfAction: 'Dual EGFR/MET inhibition',
+      evidenceLevel: 'FDA-Approved', biomarker: 'MET amplification as resistance' },
+
+    // === OLIGOMETASTATIC DISEASE TARGETS ===
+    { gene: 'Oligomet', protein: 'Oligometastatic Disease', pathway: 'Multiple',
+      cancerTypes: ['NSCLC Oligomet', 'Colorectal Liver Mets', 'Prostate Oligomet'],
+      approvedDrugs: ['SBRT', 'Metastasectomy', 'Local ablation', 'Continued systemic'],
+      mechanismOfAction: 'Consolidative local therapy',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Limited metastatic burden (1-5 mets)' },
+
+    // === THERAPY-RELATED MALIGNANCY TARGETS ===
+    { gene: 't-MN', protein: 'Therapy-Related Myeloid Neoplasm', pathway: 'Multiple',
+      cancerTypes: ['t-AML', 't-MDS'],
+      approvedDrugs: ['CPX-351 (favorable)', 'Venetoclax-HMA', 'Allogeneic transplant'],
+      mechanismOfAction: 'Intensive therapy if fit, otherwise HMA-based',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Prior chemo/radiation exposure' },
+
+    // === SPECIAL POPULATIONS ===
+    { gene: 'Organ Transplant', protein: 'Post-Transplant Malignancy', pathway: 'Multiple',
+      cancerTypes: ['PTLD', 'Skin Cancer', 'Kaposi', 'Any post-transplant'],
+      approvedDrugs: ['Reduce immunosuppression', 'Rituximab (PTLD)', 'mTOR-based IS'],
+      mechanismOfAction: 'Balance rejection risk vs cancer treatment',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Solid organ transplant recipient' },
+    { gene: 'Autoimmune', protein: 'Cancer with Autoimmune Disease', pathway: 'Immune',
+      cancerTypes: ['Any cancer with autoimmune comorbidity'],
+      approvedDrugs: ['Checkpoint inhibitors with caution', 'Targeted therapy preferred', 'Close monitoring'],
+      mechanismOfAction: 'Risk-benefit assessment for immunotherapy',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Pre-existing autoimmune disease' }
   ];
 
   // ═══════════════════════════════════════════════════════════════════════════════
@@ -1683,7 +1889,147 @@ export class CancerTreatmentCapabilityModule {
       organization: 'Other', cancerType: 'Any with Effusion', stage: 'Metastatic',
       treatmentModalities: ['Thoracentesis/Paracentesis', 'Pleurodesis', 'Indwelling Catheter', 'HIPEC (peritoneal)'],
       efficacyScore: 0.70, sideEffectProfile: ['Procedure-related'],
-      references: ['TIME trials'] }
+      references: ['TIME trials'] },
+
+    // ═══════════════════════════════════════════════════════════════════════════════
+    // SURVIVORSHIP PROTOCOLS
+    // ═══════════════════════════════════════════════════════════════════════════════
+    { id: 'survivor-breast', name: 'Breast Cancer Survivorship',
+      organization: 'ASCO', cancerType: 'Breast', stage: 'Post-Treatment',
+      treatmentModalities: ['Annual mammography', 'Endocrine therapy adherence', 'Bone health', 'Cardiac surveillance', 'Lymphedema management'],
+      efficacyScore: 0.95, sideEffectProfile: ['Long-term endocrine effects'],
+      references: ['ASCO Survivorship Guidelines'] },
+    { id: 'survivor-colorectal', name: 'Colorectal Cancer Survivorship',
+      organization: 'ASCO', cancerType: 'Colorectal', stage: 'Post-Treatment',
+      treatmentModalities: ['CEA monitoring', 'Colonoscopy surveillance', 'CT scans', 'Neuropathy management'],
+      efficacyScore: 0.90, sideEffectProfile: ['Bowel dysfunction', 'Neuropathy'],
+      references: ['ASCO Colorectal Survivorship'] },
+    { id: 'survivor-lymphoma', name: 'Lymphoma Survivorship',
+      organization: 'NCCN', cancerType: 'Lymphoma', stage: 'Post-Treatment',
+      treatmentModalities: ['Secondary malignancy screening', 'Cardiac surveillance', 'Thyroid monitoring', 'Fertility preservation follow-up'],
+      efficacyScore: 0.92, sideEffectProfile: ['Late effects of chemo/radiation'],
+      references: ['NCCN Survivorship Guidelines'] },
+    { id: 'survivor-pediatric', name: 'Pediatric Cancer Survivorship (COG LTFU)',
+      organization: 'Other', cancerType: 'Pediatric Cancers', stage: 'Long-Term Follow-Up',
+      treatmentModalities: ['Risk-based surveillance', 'Cardiac echo', 'Endocrine evaluation', 'Neurocognitive assessment', 'Secondary cancer screening', 'Fertility counseling'],
+      efficacyScore: 0.90, sideEffectProfile: ['Late effects of childhood treatment'],
+      references: ['COG Long-Term Follow-Up Guidelines'] },
+    { id: 'survivor-prostate', name: 'Prostate Cancer Survivorship',
+      organization: 'ASCO', cancerType: 'Prostate', stage: 'Post-Treatment',
+      treatmentModalities: ['PSA monitoring', 'ADT side effect management', 'Bone health', 'Sexual function support', 'Urinary continence'],
+      efficacyScore: 0.93, sideEffectProfile: ['ADT metabolic effects', 'ED'],
+      references: ['ASCO Prostate Survivorship'] },
+
+    // ═══════════════════════════════════════════════════════════════════════════════
+    // QUALITY OF LIFE PROTOCOLS
+    // ═══════════════════════════════════════════════════════════════════════════════
+    { id: 'qol-fatigue', name: 'Cancer-Related Fatigue Management',
+      organization: 'NCCN', cancerType: 'Any', stage: 'Any',
+      treatmentModalities: ['Exercise prescription', 'Sleep hygiene', 'Treat anemia/depression', 'Psychostimulants if severe'],
+      efficacyScore: 0.75, sideEffectProfile: ['Minimal'],
+      references: ['NCCN Cancer-Related Fatigue Guidelines'] },
+    { id: 'qol-pain', name: 'Cancer Pain Management',
+      organization: 'NCCN', cancerType: 'Any', stage: 'Any',
+      treatmentModalities: ['WHO Pain Ladder', 'Opioid rotation', 'Interventional procedures', 'Palliative radiation', 'Integrative approaches'],
+      efficacyScore: 0.85, sideEffectProfile: ['Opioid side effects'],
+      references: ['NCCN Adult Cancer Pain'] },
+    { id: 'qol-nausea', name: 'Chemotherapy-Induced Nausea/Vomiting',
+      organization: 'ASCO', cancerType: 'Any on Chemo', stage: 'Any',
+      treatmentModalities: ['5-HT3 antagonists', 'NK1 antagonists', 'Dexamethasone', 'Olanzapine'],
+      efficacyScore: 0.90, sideEffectProfile: ['Constipation', 'QT prolongation'],
+      references: ['ASCO Antiemetic Guidelines'] },
+    { id: 'qol-neuropathy', name: 'Chemotherapy-Induced Peripheral Neuropathy',
+      organization: 'ASCO', cancerType: 'Any', stage: 'Any',
+      treatmentModalities: ['Duloxetine', 'Gabapentin', 'Physical therapy', 'Dose modification', 'Cryotherapy (prevention)'],
+      efficacyScore: 0.60, sideEffectProfile: ['Drowsiness'],
+      references: ['ASCO CIPN Guidelines'] },
+    { id: 'qol-psychosocial', name: 'Psychosocial Distress Management',
+      organization: 'NCCN', cancerType: 'Any', stage: 'Any',
+      treatmentModalities: ['Distress screening', 'Counseling', 'Support groups', 'Psychiatry referral', 'Antidepressants/anxiolytics'],
+      efficacyScore: 0.80, sideEffectProfile: ['Medication side effects if used'],
+      references: ['NCCN Distress Management'] },
+    { id: 'qol-nutrition', name: 'Cancer Nutrition Management',
+      organization: 'Other', cancerType: 'Any', stage: 'Any',
+      treatmentModalities: ['Nutritional assessment', 'Oral supplements', 'Enteral/parenteral if needed', 'Cachexia management'],
+      efficacyScore: 0.75, sideEffectProfile: ['GI intolerance'],
+      references: ['ESPEN Cancer Nutrition Guidelines'] },
+
+    // ═══════════════════════════════════════════════════════════════════════════════
+    // SPECIAL POPULATION PROTOCOLS
+    // ═══════════════════════════════════════════════════════════════════════════════
+    { id: 'special-hiv', name: 'Cancer in HIV/AIDS Patients',
+      organization: 'NCCN', cancerType: 'Any in HIV+', stage: 'Any',
+      treatmentModalities: ['Optimize ART', 'Standard cancer treatment when possible', 'Drug-drug interaction check', 'Infectious prophylaxis'],
+      efficacyScore: 0.75, sideEffectProfile: ['Drug interactions', 'Immunosuppression'],
+      references: ['NCI HIV/AIDS Malignancy Guidelines'] },
+    { id: 'special-transplant-cancer', name: 'Cancer in Transplant Recipients',
+      organization: 'Other', cancerType: 'Any post-transplant', stage: 'Any',
+      treatmentModalities: ['Reduce immunosuppression if possible', 'Switch to mTOR inhibitor', 'Standard cancer therapy with caution', 'Consider rejection risk'],
+      efficacyScore: 0.65, sideEffectProfile: ['Rejection risk', 'Infection'],
+      references: ['Transplant oncology consensus'] },
+    { id: 'special-dialysis', name: 'Cancer in Dialysis Patients',
+      organization: 'Other', cancerType: 'Any on Dialysis', stage: 'Any',
+      treatmentModalities: ['Dose-adjusted chemotherapy', 'Dialysis timing coordination', 'RCC screening', 'Consider transplant candidacy'],
+      efficacyScore: 0.60, sideEffectProfile: ['Altered pharmacokinetics'],
+      references: ['Renal impairment dosing guidelines'] },
+    { id: 'special-liver-impaired', name: 'Cancer with Liver Dysfunction',
+      organization: 'Other', cancerType: 'Any with Liver Dysfunction', stage: 'Any',
+      treatmentModalities: ['Child-Pugh adjusted dosing', 'Avoid hepatotoxic agents', 'Close LFT monitoring'],
+      efficacyScore: 0.55, sideEffectProfile: ['Hepatotoxicity risk'],
+      references: ['Hepatic impairment dosing guidelines'] },
+    { id: 'special-adolescent-young-adult', name: 'Adolescent/Young Adult (AYA) Cancer',
+      organization: 'NCCN', cancerType: 'AYA Cancers (15-39)', stage: 'Any',
+      treatmentModalities: ['Age-appropriate protocols', 'Fertility preservation', 'Psychosocial support', 'Financial navigation', 'Transition planning'],
+      efficacyScore: 0.85, sideEffectProfile: ['Long-term survivorship issues'],
+      references: ['NCCN AYA Oncology'] },
+    { id: 'special-second-primary', name: 'Second Primary Malignancy',
+      organization: 'Other', cancerType: 'Second Primary Cancer', stage: 'Any',
+      treatmentModalities: ['Treat as new primary', 'Consider prior treatment toxicities', 'Cumulative dose limits', 'Genetic evaluation'],
+      efficacyScore: 0.70, sideEffectProfile: ['Prior treatment effects'],
+      references: ['Second malignancy management guidelines'] },
+
+    // ═══════════════════════════════════════════════════════════════════════════════
+    // ETHNIC AND POPULATION-SPECIFIC CONSIDERATIONS
+    // ═══════════════════════════════════════════════════════════════════════════════
+    { id: 'ethnic-pharmacogenomics', name: 'Pharmacogenomic-Guided Therapy',
+      organization: 'FDA', cancerType: 'Any', stage: 'Any',
+      treatmentModalities: ['DPYD testing (5-FU)', 'UGT1A1 testing (Irinotecan)', 'TPMT/NUDT15 (Thiopurines)', 'G6PD (Rasburicase)'],
+      efficacyScore: 0.90, sideEffectProfile: ['Prevents severe toxicity'],
+      references: ['CPIC Guidelines', 'FDA drug labels'] },
+    { id: 'ethnic-asian-egfr', name: 'EGFR in East Asian NSCLC',
+      organization: 'Other', cancerType: 'NSCLC (East Asian)', stage: 'Any',
+      treatmentModalities: ['Higher EGFR mutation rate (~50%)', 'First-line TKI', 'Osimertinib preferred'],
+      efficacyScore: 0.85, sideEffectProfile: ['Standard TKI toxicities'],
+      references: ['Asian NSCLC molecular epidemiology'] },
+    { id: 'ethnic-tnbc-african', name: 'TNBC in African Descent',
+      organization: 'Other', cancerType: 'TNBC (African descent)', stage: 'Any',
+      treatmentModalities: ['Higher incidence', 'Standard TNBC protocols', 'Ensure access to immunotherapy', 'Clinical trial enrollment'],
+      efficacyScore: 0.75, sideEffectProfile: ['Standard toxicities'],
+      references: ['Cancer disparities research'] },
+    { id: 'ethnic-multiple-myeloma-african', name: 'Multiple Myeloma in African Descent',
+      organization: 'Other', cancerType: 'Multiple Myeloma (African descent)', stage: 'Any',
+      treatmentModalities: ['2x higher incidence', 'Standard MM protocols', 'Consider earlier transplant', 'Equal access to novel therapies'],
+      efficacyScore: 0.75, sideEffectProfile: ['Standard toxicities'],
+      references: ['Myeloma disparities literature'] },
+
+    // ═══════════════════════════════════════════════════════════════════════════════
+    // PREVENTION AND RISK REDUCTION
+    // ═══════════════════════════════════════════════════════════════════════════════
+    { id: 'prevention-brca-rrso', name: 'BRCA Risk-Reducing Surgery',
+      organization: 'NCCN', cancerType: 'BRCA1/2 Carrier', stage: 'Prevention',
+      treatmentModalities: ['Risk-reducing salpingo-oophorectomy', 'Risk-reducing mastectomy', 'Enhanced surveillance', 'Chemoprevention options'],
+      efficacyScore: 0.95, sideEffectProfile: ['Surgical menopause', 'QoL effects'],
+      references: ['NCCN Genetic/Familial High-Risk'] },
+    { id: 'prevention-lynch-colon', name: 'Lynch Syndrome Surveillance',
+      organization: 'NCCN', cancerType: 'Lynch Syndrome', stage: 'Prevention',
+      treatmentModalities: ['Colonoscopy q1-2 years from age 20-25', 'Consider prophylactic hysterectomy/BSO', 'Aspirin (investigational)'],
+      efficacyScore: 0.85, sideEffectProfile: ['Procedural risks'],
+      references: ['NCCN Lynch Syndrome'] },
+    { id: 'prevention-fap', name: 'FAP Prophylactic Colectomy',
+      organization: 'NCCN', cancerType: 'FAP', stage: 'Prevention',
+      treatmentModalities: ['Prophylactic colectomy (late teens/early 20s)', 'Endoscopic surveillance', 'Sulindac/Celecoxib for adenomas'],
+      efficacyScore: 0.95, sideEffectProfile: ['Surgical morbidity'],
+      references: ['NCCN Colorectal Cancer Screening'] }
   ];
 
   constructor() {