@erosolaraijs/cure 2.0.0 → 2.2.0

package/src/capabilities/cancerTreatmentCapability.ts

@@ -631,7 +631,523 @@ 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' },
+
+    // === LIQUID BIOPSY AND ctDNA MONITORING ===
+    { gene: 'ctDNA', protein: 'Circulating Tumor DNA', pathway: 'Monitoring',
+      cancerTypes: ['All Solid Tumors'],
+      approvedDrugs: ['Guardant360', 'FoundationOne Liquid CDx', 'Signatera'],
+      mechanismOfAction: 'Non-invasive tumor genotyping and monitoring',
+      evidenceLevel: 'FDA-Approved', biomarker: 'ctDNA for treatment selection and MRD' },
+    { gene: 'CTC', protein: 'Circulating Tumor Cells', pathway: 'Monitoring',
+      cancerTypes: ['Breast', 'Prostate', 'Colorectal'],
+      approvedDrugs: ['CellSearch'],
+      mechanismOfAction: 'Enumerate CTCs for prognosis',
+      evidenceLevel: 'FDA-Approved', biomarker: 'CTC count ≥5 (breast/prostate)' },
+    { gene: 'MRD-Heme', protein: 'Minimal Residual Disease (Hematologic)', pathway: 'Monitoring',
+      cancerTypes: ['ALL', 'AML', 'CLL', 'Multiple Myeloma', 'Lymphoma'],
+      approvedDrugs: ['Flow cytometry', 'NGS-MRD', 'clonoSEQ'],
+      mechanismOfAction: 'Detect residual disease at 10^-6 sensitivity',
+      evidenceLevel: 'FDA-Approved', biomarker: 'MRD negativity predicts outcomes' },
+    { gene: 'MRD-Solid', protein: 'Molecular Residual Disease (Solid)', pathway: 'Monitoring',
+      cancerTypes: ['Colorectal', 'Breast', 'NSCLC', 'Bladder'],
+      approvedDrugs: ['Signatera', 'Guardant Reveal'],
+      mechanismOfAction: 'ctDNA-based MRD detection post-surgery',
+      evidenceLevel: 'FDA-Approved', biomarker: 'ctDNA MRD guides adjuvant therapy' },
+
+    // === FERTILITY PRESERVATION ===
+    { gene: 'Fertility-Female', protein: 'Female Fertility Preservation', pathway: 'Supportive',
+      cancerTypes: ['Any in reproductive-age female'],
+      approvedDrugs: ['Oocyte cryopreservation', 'Embryo cryopreservation', 'Ovarian tissue cryopreservation', 'GnRH agonist ovarian suppression'],
+      mechanismOfAction: 'Preserve reproductive potential before gonadotoxic therapy',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Pre-menopausal, desires future fertility' },
+    { gene: 'Fertility-Male', protein: 'Male Fertility Preservation', pathway: 'Supportive',
+      cancerTypes: ['Any in reproductive-age male'],
+      approvedDrugs: ['Sperm cryopreservation', 'Testicular tissue cryopreservation (pediatric)', 'Testicular sperm extraction'],
+      mechanismOfAction: 'Bank sperm before gonadotoxic therapy',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Post-pubertal male, desires future fertility' },
+    { gene: 'Gonadotoxicity', protein: 'Gonadotoxicity Assessment', pathway: 'Supportive',
+      cancerTypes: ['Any receiving gonadotoxic therapy'],
+      approvedDrugs: ['AMH testing', 'FSH/LH monitoring', 'Semen analysis'],
+      mechanismOfAction: 'Assess fertility status before/after treatment',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Alkylating agents, pelvic radiation' },
+
+    // === INTEGRATIVE ONCOLOGY ===
+    { gene: 'Integrative', protein: 'Integrative Oncology Approaches', pathway: 'Supportive',
+      cancerTypes: ['Any'],
+      approvedDrugs: ['Acupuncture (CINV, pain)', 'Meditation/mindfulness', 'Yoga', 'Massage therapy', 'Music therapy'],
+      mechanismOfAction: 'Evidence-based complementary approaches',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Patient preference, symptom management' },
+    { gene: 'Cannabis', protein: 'Medical Cannabis', pathway: 'Supportive',
+      cancerTypes: ['Any with symptoms'],
+      approvedDrugs: ['Dronabinol', 'Nabilone', 'CBD/THC products (where legal)'],
+      mechanismOfAction: 'Appetite stimulation, nausea, pain',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Refractory symptoms' },
+    { gene: 'Exercise-Onc', protein: 'Exercise Oncology', pathway: 'Supportive',
+      cancerTypes: ['Any'],
+      approvedDrugs: ['Aerobic exercise prescription', 'Resistance training', 'Prehabilitation', 'Cancer rehabilitation'],
+      mechanismOfAction: 'Improve outcomes, reduce fatigue, enhance QoL',
+      evidenceLevel: 'FDA-Approved', biomarker: 'All patients who can exercise' },
+
+    // === ADVANCED RADIATION TECHNIQUES ===
+    { gene: 'SBRT', protein: 'Stereotactic Body Radiotherapy', pathway: 'Radiation',
+      cancerTypes: ['NSCLC (early)', 'Liver mets', 'Spine mets', 'Oligometastatic'],
+      approvedDrugs: ['SBRT 3-5 fractions', 'High BED delivery'],
+      mechanismOfAction: 'Ablative doses with steep dose gradients',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Limited metastatic burden, good PS' },
+    { gene: 'SRS', protein: 'Stereotactic Radiosurgery', pathway: 'Radiation',
+      cancerTypes: ['Brain metastases', 'Meningioma', 'Acoustic neuroma'],
+      approvedDrugs: ['Single fraction SRS', 'Fractionated SRS', 'Gamma Knife', 'CyberKnife'],
+      mechanismOfAction: 'Precise high-dose brain radiation',
+      evidenceLevel: 'FDA-Approved', biomarker: '1-10 brain metastases' },
+    { gene: 'Proton', protein: 'Proton Beam Therapy', pathway: 'Radiation',
+      cancerTypes: ['Pediatric tumors', 'Skull base', 'Spine', 'Prostate', 'Ocular melanoma'],
+      approvedDrugs: ['Proton therapy', 'Pencil beam scanning'],
+      mechanismOfAction: 'Bragg peak spares distal tissues',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Pediatric, re-irradiation, critical structure proximity' },
+    { gene: 'Brachytherapy', protein: 'Brachytherapy', pathway: 'Radiation',
+      cancerTypes: ['Prostate', 'Cervical', 'Breast', 'Skin'],
+      approvedDrugs: ['LDR seeds', 'HDR brachytherapy', 'Intracavitary', 'Interstitial'],
+      mechanismOfAction: 'Internal radiation source placement',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Localized disease amenable to implant' },
+    { gene: 'FLASH-RT', protein: 'FLASH Radiotherapy', pathway: 'Radiation',
+      cancerTypes: ['Investigational for all'],
+      approvedDrugs: ['Ultra-high dose rate RT (investigational)'],
+      mechanismOfAction: 'Spares normal tissue at ultra-high dose rates',
+      evidenceLevel: 'Phase I', biomarker: 'Emerging technology' },
+
+    // === INTERVENTIONAL ONCOLOGY ===
+    { gene: 'RFA', protein: 'Radiofrequency Ablation', pathway: 'Interventional',
+      cancerTypes: ['HCC', 'Colorectal liver mets', 'RCC', 'Lung nodules'],
+      approvedDrugs: ['RFA probe', 'CT/US guidance'],
+      mechanismOfAction: 'Thermal ablation of tumors',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Tumor ≤3cm, not near critical structures' },
+    { gene: 'MWA', protein: 'Microwave Ablation', pathway: 'Interventional',
+      cancerTypes: ['HCC', 'Liver mets', 'Lung', 'Kidney'],
+      approvedDrugs: ['MWA antenna', 'CT guidance'],
+      mechanismOfAction: 'Microwave-induced coagulative necrosis',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Larger tumors than RFA' },
+    { gene: 'Cryoablation', protein: 'Cryoablation', pathway: 'Interventional',
+      cancerTypes: ['RCC', 'Prostate', 'Breast', 'Bone mets'],
+      approvedDrugs: ['Argon-helium cryoprobe'],
+      mechanismOfAction: 'Freeze-thaw cycles cause cell death',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Small renal masses, bone metastases' },
+    { gene: 'TACE', protein: 'Transarterial Chemoembolization', pathway: 'Interventional',
+      cancerTypes: ['HCC', 'Liver metastases', 'NET liver mets'],
+      approvedDrugs: ['Drug-eluting beads', 'Lipiodol + chemo'],
+      mechanismOfAction: 'Intra-arterial chemo + embolization',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Unresectable HCC, Child-Pugh A/B' },
+    { gene: 'Y90', protein: 'Yttrium-90 Radioembolization', pathway: 'Interventional',
+      cancerTypes: ['HCC', 'Colorectal liver mets', 'NET liver mets'],
+      approvedDrugs: ['TheraSphere', 'SIR-Spheres'],
+      mechanismOfAction: 'Intra-arterial radioactive microspheres',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Liver-predominant disease' },
+    { gene: 'IRE', protein: 'Irreversible Electroporation', pathway: 'Interventional',
+      cancerTypes: ['Pancreatic (locally advanced)', 'Liver', 'Prostate'],
+      approvedDrugs: ['NanoKnife'],
+      mechanismOfAction: 'Non-thermal ablation near vessels',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Tumors near critical vessels' },
+
+    // === END-OF-LIFE AND HOSPICE ===
+    { gene: 'Palliative-Goals', protein: 'Goals of Care Discussions', pathway: 'Palliative',
+      cancerTypes: ['Any advanced cancer'],
+      approvedDrugs: ['Serious illness conversation', 'Advance directives', 'POLST/MOLST'],
+      mechanismOfAction: 'Align treatment with patient values',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Advanced cancer, prognosis <1 year' },
+    { gene: 'Hospice', protein: 'Hospice Care', pathway: 'Palliative',
+      cancerTypes: ['Any with prognosis ≤6 months'],
+      approvedDrugs: ['Symptom management', 'Psychosocial support', 'Spiritual care', 'Bereavement'],
+      mechanismOfAction: 'Comfort-focused care at end of life',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Prognosis ≤6 months, comfort focus' },
+    { gene: 'Palliative-Sedation', protein: 'Palliative Sedation', pathway: 'Palliative',
+      cancerTypes: ['Refractory suffering at end of life'],
+      approvedDrugs: ['Midazolam', 'Propofol', 'Phenobarbital'],
+      mechanismOfAction: 'Reduce consciousness for refractory symptoms',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Refractory symptoms, imminent death' },
+
+    // === CAREGIVER SUPPORT ===
+    { gene: 'Caregiver', protein: 'Caregiver Support', pathway: 'Supportive',
+      cancerTypes: ['Any'],
+      approvedDrugs: ['Caregiver assessment', 'Respite care', 'Support groups', 'Counseling', 'Financial assistance'],
+      mechanismOfAction: 'Support informal caregivers',
+      evidenceLevel: 'FDA-Approved', biomarker: 'All cancer patients with caregivers' },
+
+    // === FINANCIAL TOXICITY ===
+    { gene: 'Financial', protein: 'Financial Toxicity Mitigation', pathway: 'Supportive',
+      cancerTypes: ['Any'],
+      approvedDrugs: ['Copay assistance', 'Patient assistance programs', 'Social work', 'Financial navigation', 'Generic alternatives'],
+      mechanismOfAction: 'Reduce financial burden of cancer care',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Any patient with cost concerns' },
+
+    // === RARE HISTOLOGIC SUBTYPES ===
+    { gene: 'Carcinosarcoma', protein: 'Carcinosarcoma/MMMT', pathway: 'Multiple',
+      cancerTypes: ['Uterine carcinosarcoma', 'Ovarian carcinosarcoma'],
+      approvedDrugs: ['Carboplatin/Paclitaxel', 'Ifosfamide', 'Pembrolizumab'],
+      mechanismOfAction: 'Treat as high-grade carcinoma',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Biphasic tumor' },
+    { gene: 'Adenoid-Cystic', protein: 'Adenoid Cystic Carcinoma', pathway: 'Multiple',
+      cancerTypes: ['Salivary gland', 'Breast', 'Skin', 'Tracheobronchial'],
+      approvedDrugs: ['Surgery + radiation', 'Lenvatinib (investigational)', 'Axitinib'],
+      mechanismOfAction: 'Slow-growing but persistent disease',
+      evidenceLevel: 'Phase II', biomarker: 'MYB-NFIB fusion common' },
+    { gene: 'Clear-Cell-Sarc', protein: 'Clear Cell Sarcoma', pathway: 'Fusion',
+      cancerTypes: ['Soft tissue (tendons)'],
+      approvedDrugs: ['Surgery', 'Chemotherapy (limited efficacy)', 'Clinical trials'],
+      mechanismOfAction: 'EWSR1-ATF1 fusion driven',
+      evidenceLevel: 'Phase II', biomarker: 'EWSR1-ATF1/CREB1 fusion' },
+    { gene: 'Alveolar-Soft', protein: 'Alveolar Soft Part Sarcoma', pathway: 'Fusion',
+      cancerTypes: ['Soft tissue (extremities)'],
+      approvedDrugs: ['Atezolizumab', 'Sunitinib', 'Axitinib'],
+      mechanismOfAction: 'ASPL-TFE3 fusion, responds to anti-angiogenics/IO',
+      evidenceLevel: 'FDA-Approved', biomarker: 'ASPL-TFE3 fusion' },
+    { gene: 'PEComa', protein: 'Perivascular Epithelioid Cell Tumor', pathway: 'mTOR',
+      cancerTypes: ['Soft tissue', 'GI', 'Gynecologic'],
+      approvedDrugs: ['Sirolimus', 'Nab-sirolimus'],
+      mechanismOfAction: 'TSC/mTOR pathway driven',
+      evidenceLevel: 'FDA-Approved', biomarker: 'TSC1/2 alteration' },
+    { gene: 'GNET', protein: 'Gastrointestinal Neuroectodermal Tumor', pathway: 'Fusion',
+      cancerTypes: ['GI tract (rare)'],
+      approvedDrugs: ['Surgery', 'Sarcoma-type chemotherapy'],
+      mechanismOfAction: 'EWSR1-CREB1 fusion',
+      evidenceLevel: 'Phase II', biomarker: 'EWSR1 rearrangement' },
+    { gene: 'Phyllodes', protein: 'Phyllodes Tumor', pathway: 'Breast',
+      cancerTypes: ['Breast (fibroepithelial)'],
+      approvedDrugs: ['Wide excision', 'Mastectomy if needed', 'Radiation (borderline/malignant)'],
+      mechanismOfAction: 'Surgical resection primary',
+      evidenceLevel: 'FDA-Approved', biomarker: 'MED12 mutation common' },
+    { gene: 'Secretory-Breast', protein: 'Secretory Breast Carcinoma', pathway: 'Fusion',
+      cancerTypes: ['Breast (rare, often pediatric)'],
+      approvedDrugs: ['Surgery', 'Larotrectinib/Entrectinib if TRK+'],
+      mechanismOfAction: 'ETV6-NTRK3 fusion in most cases',
+      evidenceLevel: 'FDA-Approved', biomarker: 'ETV6-NTRK3 fusion' },
+    { gene: 'Inflammatory-Breast', protein: 'Inflammatory Breast Cancer', pathway: 'Aggressive',
+      cancerTypes: ['Breast (IBC)'],
+      approvedDrugs: ['Neoadjuvant chemo mandatory', 'Mastectomy', 'Radiation', 'Targeted/IO per subtype'],
+      mechanismOfAction: 'Trimodality therapy required',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Clinical diagnosis (peau d\'orange)' },
+    { gene: 'Small-Cell-Ovarian', protein: 'Small Cell Ovarian (Hypercalcemic)', pathway: 'SMARCA4',
+      cancerTypes: ['Ovary (young women)'],
+      approvedDrugs: ['Intensive chemo', 'EZH2 inhibitors (investigational)', 'Clinical trials'],
+      mechanismOfAction: 'SMARCA4/BRG1 loss',
+      evidenceLevel: 'Phase II', biomarker: 'SMARCA4 mutation' },
+    { gene: 'Signet-Ring', protein: 'Signet Ring Cell Carcinoma', pathway: 'Aggressive',
+      cancerTypes: ['Gastric', 'Colorectal', 'Appendiceal', 'Breast'],
+      approvedDrugs: ['Chemotherapy (often resistant)', 'HIPEC (appendiceal)'],
+      mechanismOfAction: 'Aggressive, chemoresistant histology',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Signet ring morphology' },
+    { gene: 'Plasmablastic', protein: 'Plasmablastic Lymphoma', pathway: 'Aggressive',
+      cancerTypes: ['NHL (HIV-associated, oral)'],
+      approvedDrugs: ['EPOCH', 'CODOX-M/IVAC', 'Bortezomib-based', 'CAR-T (investigational)'],
+      mechanismOfAction: 'Aggressive, often EBV+',
+      evidenceLevel: 'Phase II', biomarker: 'HIV+, EBV+' },
+    { gene: 'Blastic-NK', protein: 'Blastic Plasmacytoid Dendritic Cell Neoplasm', pathway: 'Aggressive',
+      cancerTypes: ['Skin/hematologic'],
+      approvedDrugs: ['Tagraxofusp', 'ALL-type induction', 'Transplant'],
+      mechanismOfAction: 'CD123-targeting therapy',
+      evidenceLevel: 'FDA-Approved', biomarker: 'CD123+ BPDCN' },
+
+    // === CLINICAL TRIAL MATCHING OPTIMIZATION ===
+    { gene: 'TrialMatch-Biomarker', protein: 'Biomarker-Driven Trial Matching', pathway: 'Clinical Trials',
+      cancerTypes: ['All Solid Tumors', 'All Hematologic'],
+      approvedDrugs: ['NCI-MATCH', 'NCI-MPACT', 'TAPUR', 'My Pathway', 'Molecular Analysis for Therapy Choice'],
+      mechanismOfAction: 'Match patients to trials based on actionable alterations',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Any actionable genomic alteration' },
+    { gene: 'TrialMatch-Immunotherapy', protein: 'Immunotherapy Trial Matching', pathway: 'Clinical Trials',
+      cancerTypes: ['All Solid Tumors'],
+      approvedDrugs: ['I-SPY 2', 'KEYNOTE trials', 'CheckMate trials', 'LEAP trials', 'MORPHEUS trials'],
+      mechanismOfAction: 'Novel immunotherapy combinations and sequences',
+      evidenceLevel: 'Phase III', biomarker: 'PD-L1, TMB-H, MSI-H, TILs' },
+    { gene: 'TrialMatch-ADC', protein: 'ADC Clinical Trial Matching', pathway: 'Clinical Trials',
+      cancerTypes: ['Breast', 'NSCLC', 'Bladder', 'Ovarian', 'Gastric'],
+      approvedDrugs: ['DESTINY trials', 'TROPION trials', 'PADCEV trials', 'Dato-DXd trials'],
+      mechanismOfAction: 'Next-generation antibody-drug conjugates',
+      evidenceLevel: 'Phase II', biomarker: 'HER2-low, TROP2, Nectin-4, FRα' },
+    { gene: 'TrialMatch-Bispecific', protein: 'Bispecific Antibody Trial Matching', pathway: 'Clinical Trials',
+      cancerTypes: ['Multiple Myeloma', 'Lymphoma', 'Solid Tumors'],
+      approvedDrugs: ['GPRC5D trials', 'FcRH5 trials', 'PSMA bispecific trials', 'DLL3 trials'],
+      mechanismOfAction: 'T-cell engaging bispecific antibodies',
+      evidenceLevel: 'Phase II', biomarker: 'Target antigen expression' },
+    { gene: 'TrialMatch-CART', protein: 'CAR-T/Cell Therapy Trial Matching', pathway: 'Clinical Trials',
+      cancerTypes: ['B-ALL', 'DLBCL', 'Multiple Myeloma', 'Solid Tumors'],
+      approvedDrugs: ['Allogeneic CAR-T trials', 'CAR-NK trials', 'TIL expansion trials', 'TCR-T trials'],
+      mechanismOfAction: 'Next-generation cellular therapies',
+      evidenceLevel: 'Phase I', biomarker: 'Relapsed/refractory, target antigen+' },
+    { gene: 'TrialMatch-Targeted', protein: 'Novel Targeted Therapy Trials', pathway: 'Clinical Trials',
+      cancerTypes: ['All Solid Tumors'],
+      approvedDrugs: ['KRAS G12D trials', 'SHP2 inhibitor trials', 'SOS1 inhibitor trials', 'CDK2 trials', 'WRN trials'],
+      mechanismOfAction: 'Emerging targeted therapy combinations',
+      evidenceLevel: 'Phase I', biomarker: 'KRAS G12D, STK11, KEAP1, MSS' },
+    { gene: 'TrialMatch-Degrader', protein: 'Protein Degrader Trial Matching', pathway: 'Clinical Trials',
+      cancerTypes: ['Breast', 'Prostate', 'Hematologic'],
+      approvedDrugs: ['PROTAC trials', 'Molecular glue trials', 'ER degrader trials', 'AR degrader trials'],
+      mechanismOfAction: 'Targeted protein degradation strategies',
+      evidenceLevel: 'Phase I', biomarker: 'ER+, AR+, undruggable targets' },
+    { gene: 'TrialMatch-RadioLigand', protein: 'Radioligand Therapy Trials', pathway: 'Clinical Trials',
+      cancerTypes: ['Prostate', 'NET', 'Gastric', 'Multiple Myeloma'],
+      approvedDrugs: ['FAP-targeted trials', 'PSMA tandem trials', 'Alpha-emitter trials', 'Actinium-225 trials'],
+      mechanismOfAction: 'Next-generation radiopharmaceuticals',
+      evidenceLevel: 'Phase II', biomarker: 'PSMA+, SSTR2+, FAP+' },
+    { gene: 'TrialMatch-Vaccine', protein: 'Cancer Vaccine Trial Matching', pathway: 'Clinical Trials',
+      cancerTypes: ['Melanoma', 'NSCLC', 'Pancreatic', 'Colorectal'],
+      approvedDrugs: ['mRNA neoantigen trials', 'Personalized vaccine trials', 'Viral vector trials', 'DC vaccine trials'],
+      mechanismOfAction: 'Therapeutic cancer vaccines',
+      evidenceLevel: 'Phase II', biomarker: 'Neoantigen burden, immunogenic tumors' },
+    { gene: 'TrialMatch-Epigenetic', protein: 'Epigenetic Therapy Trials', pathway: 'Clinical Trials',
+      cancerTypes: ['AML', 'MDS', 'Lymphoma', 'Solid Tumors'],
+      approvedDrugs: ['Menin inhibitor trials', 'EZH2 inhibitor trials', 'LSD1 inhibitor trials', 'BET inhibitor trials'],
+      mechanismOfAction: 'Epigenetic modulation strategies',
+      evidenceLevel: 'Phase II', biomarker: 'MLL-rearranged, NPM1, IDH' },
+    { gene: 'TrialMatch-Rare', protein: 'Rare Cancer Trial Matching', pathway: 'Clinical Trials',
+      cancerTypes: ['Rare Cancers', 'Ultra-Rare Histologies'],
+      approvedDrugs: ['CREATE trials', 'DART trials', 'NCI-COG Pediatric MATCH', 'RARE-1 trials'],
+      mechanismOfAction: 'Dedicated rare cancer trial networks',
+      evidenceLevel: 'Phase II', biomarker: 'Rare histology, limited treatment options' },
+    { gene: 'TrialMatch-Combo', protein: 'Rational Combination Trials', pathway: 'Clinical Trials',
+      cancerTypes: ['All Solid Tumors'],
+      approvedDrugs: ['IO + targeted trials', 'Dual checkpoint trials', 'Chemo + IO + targeted trials'],
+      mechanismOfAction: 'Synergistic combination development',
+      evidenceLevel: 'Phase II', biomarker: 'Based on mechanism and biomarker' },
+    { gene: 'TrialMatch-Neoadjuvant', protein: 'Neoadjuvant/Adjuvant Trials', pathway: 'Clinical Trials',
+      cancerTypes: ['Breast', 'NSCLC', 'Melanoma', 'RCC', 'Bladder'],
+      approvedDrugs: ['Perioperative IO trials', 'ctDNA-guided trials', 'De-escalation trials'],
+      mechanismOfAction: 'Optimize perioperative therapy',
+      evidenceLevel: 'Phase III', biomarker: 'Resectable, high-risk features' },
+    { gene: 'TrialMatch-ctDNA', protein: 'ctDNA-Guided Therapy Trials', pathway: 'Clinical Trials',
+      cancerTypes: ['Colorectal', 'Breast', 'NSCLC', 'Bladder', 'All Solid'],
+      approvedDrugs: ['CIRCULATE trials', 'DYNAMIC trials', 'ctDNA escalation trials', 'MRD-directed trials'],
+      mechanismOfAction: 'ctDNA-based treatment decisions',
+      evidenceLevel: 'Phase III', biomarker: 'ctDNA MRD status post-surgery' },
+    { gene: 'TrialMatch-Pediatric', protein: 'Pediatric Cancer Trial Matching', pathway: 'Clinical Trials',
+      cancerTypes: ['Pediatric Solid Tumors', 'Pediatric Brain Tumors', 'Pediatric Leukemia'],
+      approvedDrugs: ['COG trials', 'PBTC trials', 'Pediatric MATCH', 'PPTP agent trials'],
+      mechanismOfAction: 'Age-appropriate pediatric trials',
+      evidenceLevel: 'Phase I', biomarker: 'Age ≤21, pediatric-specific alterations' },
+    { gene: 'TrialMatch-AYA', protein: 'AYA-Specific Trial Matching', pathway: 'Clinical Trials',
+      cancerTypes: ['AYA Cancers (15-39 years)'],
+      approvedDrugs: ['AYA-focused protocols', 'Adolescent-friendly trial sites', 'Fertility-preserving trials'],
+      mechanismOfAction: 'Age-appropriate trial design for young adults',
+      evidenceLevel: 'Phase II', biomarker: 'Age 15-39, unique AYA biology' },
+    { gene: 'TrialMatch-Elderly', protein: 'Elderly/Frail Patient Trials', pathway: 'Clinical Trials',
+      cancerTypes: ['All Cancers in Elderly'],
+      approvedDrugs: ['Geriatric oncology trials', 'De-intensification trials', 'Tolerability-focused trials'],
+      mechanismOfAction: 'Appropriate trials for older adults',
+      evidenceLevel: 'Phase II', biomarker: 'Age ≥70, comorbidities, frailty' },
+    { gene: 'TrialMatch-RealWorld', protein: 'Real-World Evidence Integration', pathway: 'Clinical Trials',
+      cancerTypes: ['All Cancers'],
+      approvedDrugs: ['Pragmatic trial designs', 'Registry-embedded trials', 'EHR-integrated trials'],
+      mechanismOfAction: 'Real-world data to expand trial access',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Broader eligibility criteria' },
+    { gene: 'TrialMatch-Access', protein: 'Clinical Trial Access Solutions', pathway: 'Clinical Trials',
+      cancerTypes: ['All Cancers'],
+      approvedDrugs: ['Decentralized trials', 'Travel support programs', 'Community site trials', 'Virtual trial visits'],
+      mechanismOfAction: 'Remove barriers to trial participation',
+      evidenceLevel: 'FDA-Approved', biomarker: 'Geographic/financial barriers' }
   ];
 
   // ═══════════════════════════════════════════════════════════════════════════════
@@ -1683,7 +2199,147 @@ 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() {