Principles of Cancer Therapy

Goals & Staging - Cancer Battle Plan

• Therapeutic Goals:
  • Curative: Aim for complete cancer eradication.
  • Palliative: Focus on symptom relief & improving QoL.
  • Adjuvant: Post-primary Rx (e.g., surgery) to target micrometastases, ↓recurrence risk.
  • Neoadjuvant: Pre-primary Rx to shrink tumor, ↑resectability/organ preservation.
• Staging: Defines anatomical extent; crucial for Rx planning & prognosis.
  • Types: Clinical (cTNM), Pathological (pTNM), Post-therapy (ypTNM).
  • TNM System:
    • T: Primary Tumor (size, extent).
    • N: Regional Lymph Nodes.
    • M: Distant Metastasis.

  ⭐ Pathological staging (pTNM), based on surgical specimen, is generally more accurate than clinical staging (cTNM).

Surgical Oncology - Scalpel's Edge

• Core Principle: Primary curative modality for many solid tumors. Aims for complete tumor removal with adequate margins.
• Resection Status (Microscopic Assessment):
  • R0: No tumor at margin (goal for cure).
  • R1: Microscopic tumor at margin.
  • R2: Macroscopic residual tumor.
• Surgical Margins: Negative margins crucial for local control. Width varies by tumor type (e.g., Basal Cell Carcinoma 3-5 mm; Sarcoma 1-2 cm).

⭐ R0 resection (microscopically clear margins) is the most significant predictor of local control and survival for most solid tumors treated with curative intent.

• 📌 Mnemonic (Types): "Doctors Seek Cure Patiently, Preventing Disease." (Diagnostic, Staging, Curative, Palliative, Prophylactic, Debulking)

Radiation & Chemo - Systemic & Local Strikes

Radiation Therapy (RT): Localized tumor destruction via DNA damage.

• Delivery:
  • External Beam (EBRT): Teletherapy (IMRT, SBRT).
  • Brachytherapy: Internal, sealed source near/in tumor.
• Principles:
  • Fractionation: Standard 1.8-2 Gy/day. Spares normal tissue (repair, reoxygenation).
  • Radiosensitizers (e.g., 5-FU, Cisplatin) ↑ tumor response.
  • Radioprotectors (e.g., Amifostine) shield normal cells.
• Toxicity: Acute (mucositis), Late (fibrosis).

Chemotherapy (CTx): Systemic, targets rapidly dividing cells.

• Types:
  • Cell Cycle Specific (CCS): Act on specific phase (Antimetabolites - S; Vincas - M).
  • Cell Cycle Non-Specific (CCNS): Act on all phases (Alkylating agents, Platinum).
• Key Drugs & Toxicities:
  • Alkylating: Cyclophosphamide (hemorrhagic cystitis; 📌 MESNA).
  • Platinum: Cisplatin (nephro/oto/neurotoxic).
  • Antimetabolites: Methotrexate (myelosuppression; Leucovorin rescue).
  • Antitumor Abx: Doxorubicin (cardiotoxic).
• Combination CTx: ↑ efficacy, ↓ resistance.

![Image placeholder: Cell cycle phases and sites of action for chemotherapy drugs]

⭐ Vincristine: peripheral neuropathy (dose-limiting). Vinblastine: myelosuppressive. (📌 VinCristine = CNS; VinBlastine = Bone marrow).

Targeted & Immune Tx - Precision Warfare

• Hormonal Therapy: Modulates hormone-driven cancers.
  • Breast Ca: Tamoxifen (SERM), Aromatase Inhibitors (e.g., Letrozole).
  • Prostate Ca: Anti-androgens (e.g., Bicalutamide), GnRH analogs (e.g., Leuprolide).
• Targeted Therapy: Acts on specific molecular targets; often identified by "-mab" or "-nib" suffixes.
  • Monoclonal Antibodies (mAbs): E.g., Trastuzumab (targets HER2 in Breast Ca), Rituximab (targets CD20 on B-cells).
  • Tyrosine Kinase Inhibitors (TKIs): E.g., Imatinib (targets BCR-ABL in CML).
• Immunotherapy: Enhances host anti-tumor immunity.
  • Checkpoint Inhibitors: Release "brakes" on T-cells.
    • PD-1 inhibitors: Nivolumab, Pembrolizumab.
    • PD-L1 inhibitors: Atezolizumab.
    • CTLA-4 inhibitors: Ipilimumab.

  ⭐ Trastuzumab (anti-HER2 mAb) requires baseline and periodic cardiac function monitoring (e.g., LVEF) due to risk of cardiotoxicity.

• CAR T-cell therapy: Genetically engineered T-cells to fight cancer (e.g., hematologic malignancies).

High‑Yield Points - ⚡ Biggest Takeaways

• Adjuvant therapy aims to eradicate micrometastases after primary treatment.
• Neoadjuvant therapy is administered before definitive local therapy to improve outcomes.
• Palliative therapy focuses on symptom control and enhancing quality of life in advanced cancer.
• Chemotherapy targets rapidly dividing cells, leading to systemic side effects.
• Radiotherapy utilizes ionizing radiation to induce DNA damage in cancer cells.
• Hormonal therapy is crucial for hormone-sensitive tumors like breast and prostate cancer.
• Targeted therapies act on specific molecular abnormalities within cancer cells.