Adjuvant Therapies

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Introduction - Adjuvant Aces

  • Adjuvant therapy: Additional cancer treatment given after the primary treatment (usually surgery) to target residual microscopic disease.
  • Core Aims:
    • Eradicate micrometastases.
    • Improve local tumour control.
    • Reduce recurrence risk (local & systemic).
    • Enhance overall survival (OS) & disease-free survival (DFS).
  • Key Modalities: Chemotherapy, Radiotherapy.
  • Crucial for high-grade sarcomas (e.g., Osteosarcoma, Ewing's sarcoma).

⭐ For osteosarcoma, multi-agent adjuvant chemotherapy improves 5-year survival from <20% to ~65%.

Chemotherapy - Chemo Crusaders

Targets micrometastases. Neoadjuvant: shrinks tumor, assesses response. Adjuvant: eradicates residual disease.

  • Osteosarcoma:
    • Regimen: MAP (Methotrexate, Adriamycin/Doxorubicin, Cisplatin)
    • High-dose Methotrexate requires Leucovorin rescue.
  • Ewing's Sarcoma:
    • Regimen: VDC/IE (Vincristine, Doxorubicin, Cyclophosphamide alternating with Ifosfamide, Etoposide)
  • Key Drugs & Toxicities:
    • Doxorubicin: Cardiotoxicity (max lifetime dose 450-550 mg/m²). 📌 "Ruby Red Heart".
    • Cisplatin: Nephrotoxicity, ototoxicity.
    • Ifosfamide/Cyclophosphamide: Hemorrhagic cystitis (prevent with Mesna).
    • Vincristine: Peripheral neuropathy (dose-limiting).
    • Methotrexate: Myelosuppression, mucositis.

Common Chemotherapy Side Effects

⭐ High-dose methotrexate with leucovorin rescue is a cornerstone in osteosarcoma treatment, significantly improving survival rates by allowing for higher, more effective methotrexate doses while protecting normal cells.

Radiotherapy - Radiation Rangers

  • Goal: Achieve local tumor control; used pre-operatively, post-operatively, or definitively for unresectable tumors.
  • Indications:
    • Ewing's sarcoma (highly sensitive).
    • Soft Tissue Sarcomas (STS): Especially for close/positive margins post-resection, or large/deep tumors pre-operatively.
    • Metastatic disease: Palliation of pain (e.g., bone metastases).
    • Giant Cell Tumor (aggressive/recurrent).
  • Types & Doses:
    • External Beam RT (EBRT): Most common. Curative intent: 50-70 Gy.
    • Intensity Modulated RT (IMRT): Spares normal tissues better.
    • Brachytherapy: Radioactive sources placed directly into/near tumor bed.
    • Palliative RT: e.g., 8 Gy single fraction or 30 Gy in 10 fractions.
  • Acute Side Effects: Skin reactions (erythema, desquamation), fatigue, mucositis.
  • Chronic Side Effects: Fibrosis, lymphedema, pathological fracture, radiation-induced sarcoma. 📌 Mnemonic: "Fibro Lympho And Pathologic Sarcoma" (FLAPS).

⭐ Ewing's sarcoma is highly radiosensitive and radiotherapy forms a crucial part of its multimodality treatment, often used for definitive local control or after surgery if margins are inadequate. Osteosarcomas are generally considered radioresistant.

Targeted & Biologics - Precision Players

  • Targeted Therapy: Exploits specific tumor molecular pathways.
    • TKIs (e.g., Pazopanib): For some sarcomas.
    • mTOR inhibitors (e.g., Everolimus).
    • CDK4/6 inhibitors (e.g., Palbociclib).
  • Immunotherapy: Enhances anti-tumor immune response.
    • Checkpoint inhibitors (PD-1/PD-L1): Investigational in some sarcomas.
  • Bone-Modifying Agents (BMAs): Vital for bone health & tumor control.
    • Bisphosphonates (e.g., Zoledronic acid): Inhibit osteoclasts; for bone mets, GCT.
    • Denosumab (Anti-RANKL mAb): Suppresses osteoclasts. Key for GCT, bone mets.

      ⭐ Denosumab is pivotal for Giant Cell Tumor (GCT), directly targeting RANKL to curb bone resorption.

High‑Yield Points - ⚡ Biggest Takeaways

  • Neoadjuvant chemotherapy for osteosarcoma & Ewing's sarcoma improves resectability and targets micrometastases.
  • Adjuvant chemotherapy (post-op) significantly boosts survival in osteosarcoma & Ewing's sarcoma.
  • MAP regimen (Methotrexate, Doxorubicin, Cisplatin) is standard for osteosarcoma.
  • VDC/IE regimen (Vincristine, Doxorubicin, Cyclophosphamide alternating with Ifosfamide, Etoposide) is standard for Ewing's sarcoma.
  • Radiotherapy is crucial for Ewing's sarcoma (highly radiosensitive) and for local control with positive/close margins.
  • Denosumab is effective for unresectable or recurrent Giant Cell Tumors (GCT) of bone.
  • Imatinib shows efficacy in chordomas and desmoid tumors with specific molecular targets (e.g., KIT/PDGFRA).

Practice Questions: Adjuvant Therapies

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Many drugs are used as rescue therapy for preventing the adverse effects of anticancer drugs. Folinic acid is used in:-

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Flashcards: Adjuvant Therapies

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If the pain due to the lesion is functional, it is given a score of _____ according to Mirel's criteria

TAP TO REVEAL ANSWER

If the pain due to the lesion is functional, it is given a score of _____ according to Mirel's criteria

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