Principles of Cancer Therapy

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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).

Surgical Margins: R0, R1, R2, Radical, Wide, Intralesional

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). Trastuzumab-deruxtecan mechanism of action
    • 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.
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Practice Questions: Principles of Cancer Therapy

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Which of the following stages of Breast Cancer corresponds to the following features: a breast mass of 6 x 3 cm, ipsilateral supraclavicular lymph node involvement, and distant metastasis that cannot be assessed?

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Flashcards: Principles of Cancer Therapy

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Carcinoid tumors measuring >_____ cm should be managed with _____.

TAP TO REVEAL ANSWER

Carcinoid tumors measuring >_____ cm should be managed with _____.

2; hemicolectomy

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