<?xml version="1.0" encoding="UTF-8"?>
<opml version="2.0">
  <head>
    <title>040-02 Tumour evolution, biomarker reasoning, treatment resistance, and oncological emergencies</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Tumour evolution, biomarkers, resistance, emergencies">
      <outline text="Tumour evolution">
        <outline text="Evolving ecosystem, not uniform mass">
          <outline text="Descendants gain genetic, epigenetic, phenotypic change"/>
          <outline text="Hypoxia, immunity, treatment select variants"/>
        </outline>
        <outline text="Biopsy samples one region at one time">
          <outline text="Metastasis or relapse clone may differ"/>
        </outline>
        <outline text="Drivers create dependencies"/>
        <outline text="Repair loss gives predictive patterns">
          <outline text="Mismatch-repair instability, defective recombination"/>
        </outline>
        <outline text="Pathogenic label not proof of active driver">
          <outline text="Allele fraction, copy number, clonality, context"/>
        </outline>
      </outline>
      <outline text="Stress tolerance and metabolism">
        <outline text="Telomeres, checkpoint evasion, apoptosis resistance"/>
        <outline text="Metabolism supplies nucleotides, lipids, reducing power"/>
        <outline text="Aerobic glycolysis diverts carbon into biomass"/>
        <outline text="Dependence on a nutrient or repair pathway">
          <outline text="Therapeutic window"/>
        </outline>
        <outline text="Normal proliferating tissues share needs">
          <outline text="Marrow, mucosal, hair, gonadal toxicity"/>
        </outline>
      </outline>
      <outline text="Microenvironment">
        <outline text="Fibroblasts stiffen matrix, restrict access"/>
        <outline text="Macrophages kill or support tumour by signals"/>
        <outline text="Hypoxia selects acidosis-tolerant cells"/>
        <outline text="Abnormal vessels leak, shunt, collapse">
          <outline text="Uneven drug delivery"/>
          <outline text="Sanctuaries for resistant cells"/>
        </outline>
      </outline>
      <outline text="Invasion, metastasis, dormancy">
        <outline text="Loss of polarity and adhesion, motility"/>
        <outline text="Each metastatic step inefficient"/>
        <outline text="Pre-metastatic niche prepared before arrival"/>
        <outline text="Tropism reflects circulation and compatibility"/>
        <outline text="Dormant cells reactivate after years">
          <outline text="Surgery cannot prove microscopic absence"/>
          <outline text="Adjuvant therapy when risk justifies toxicity"/>
        </outline>
        <outline text="Neoadjuvant shrinks and reveals sensitivity">
          <outline text="Progression on therapy exposes resistance"/>
        </outline>
      </outline>
      <outline text="Immunity and immune toxicity">
        <outline text="Immunity constrains and shapes cancer">
          <outline text="Selection favours antigen loss and exclusion"/>
        </outline>
        <outline text="Checkpoint blockade restores existing T cells">
          <outline text="Durable only if antigen, presentation, trafficking"/>
        </outline>
        <outline text="Immune-related events during or after treatment">
          <outline text="Grade promptly, exclude infection and progression"/>
          <outline text="Steroids matched to severity"/>
          <outline text="Hormone deficiency may be permanent"/>
        </outline>
        <outline text="Mild symptoms do not prove organ safety">
          <outline text="Myocarditis, pneumonitis, adrenal crisis fatal"/>
          <outline text="Treat instability without waiting"/>
        </outline>
        <outline text="Prolonged steroids: prophylaxis, glucose, bone"/>
      </outline>
      <outline text="Tissue diagnosis">
        <outline text="Representative tissue obtained safely">
          <outline text="Avoid contaminating planes, fracture, seeding"/>
        </outline>
        <outline text="Core tissue preserves architecture"/>
        <outline text="Cytology may exhaust material"/>
        <outline text="Fixation and decalcification impair assays"/>
        <outline text="Pre-biopsy: coagulation, antithrombotics, bleeding"/>
        <outline text="Image-guided viable margin, not necrotic centre"/>
        <outline text="Lymphoma: preserve architecture"/>
        <outline text="Sarcoma: route allowing en bloc excision"/>
      </outline>
      <outline text="Grade, markers, and response">
        <outline text="Grade, stage, molecular subtype are distinct"/>
        <outline text="Prognostic versus predictive markers">
          <outline text="Association does not prove targeting helps"/>
        </outline>
        <outline text="Treatment can enlarge lesions without progression"/>
        <outline text="Stable size may hide biological response"/>
        <outline text="Markers vary with inflammation and clearance">
          <outline text="Low-risk marker screening causes overdiagnosis"/>
        </outline>
      </outline>
      <outline text="Local and cytotoxic therapy">
        <outline text="Surgery cures if all clonogenic disease removed">
          <outline text="Margins depend on biology and anatomy"/>
        </outline>
        <outline text="Node assessment risks lymphoedema, nerve injury"/>
        <outline text="Fractionation exploits repair and reoxygenation"/>
        <outline text="Late fibrosis and second cancers years later"/>
        <outline text="Combinations reduce resistant clone survival">
          <outline text="Overlapping toxicity constrains dose"/>
        </outline>
        <outline text="Vesicant extravasation needs immediate care"/>
      </outline>
      <outline text="Targeted and endocrine therapy">
        <outline text="Works only when target present and necessary"/>
        <outline text="Resistance pre-exists or emerges">
          <outline text="Target mutation, bypass, transformation"/>
        </outline>
        <outline text="Targeted means selection, not harmlessness"/>
        <outline text="Progression: check adherence, pseudoprogression">
          <outline text="Few sites escaped: add local treatment"/>
          <outline text="Negative liquid biopsy not proof of absence"/>
        </outline>
        <outline text="Endocrine therapy withdraws hormone signals">
          <outline text="Bone loss, insulin resistance, vasomotor effects"/>
        </outline>
      </outline>
      <outline text="Emergencies and survivorship">
        <outline text="Treat physiology before complete histology"/>
        <outline text="Cord compression: timed record, full spine imaging"/>
        <outline text="Hypercalcaemia: rehydrate, bridge antiresorptive delay"/>
        <outline text="Vena-cava obstruction: secure tissue if stable">
          <outline text="Airway or cerebral crisis takes priority"/>
        </outline>
        <outline text="Palliative care from diagnosis"/>
        <outline text="Screening only if benefit outweighs harms"/>
        <outline text="Treatment summary assigns follow-up responsibility"/>
      </outline>
    </outline>
  </body>
</opml>
