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The ultimate determinant of the efficacy of any anticancer therapy is the therapeutic ratio. The therapeutic ratio for a given dose of radiation therapy (RT) is defined as the ratio of the tumor control rate to the observed normal tissue toxicity. The larger this ratio is, the better tolerated the treatment is at any given dose. Indeed, the “definitive” therapeutic dose for most solid tumors has been determined by the clinically observed radiotolerance of the surrounding normal tissues, not the dose required for tumor sterilization. Therefore, with an understanding of acute and chronic toxicities of radiation, one can potentially improve the therapeutic ratio through effective intervention

Factors Affecting Side-Effect Profile


  • The location of the primary tumor and its proximity to critical structures

  • The tolerance of the surrounding normal tissue to RT

  • The associated use of other modalities of therapy such as surgery or chemotherapy


  • The arrangement and energy of the radiation beams and the anatomic structures in their path



  • The tissue response to RT at the molecular level

  • The individual's biological sensitivity to radiation

Radiation Side Effects: Acute and Late Phases

Early or acute side effects

  • Largely represent killing of rapidly proliferating cells, such as the epithelial lining of mucosal surfaces, skin, and bone marrow

  • Occur during or shortly after RT

  • Usually begin 2–3 weeks into RT, increase progressively, and resolve after completion of radiotherapy

  • A majority recover without long-term sequelae because of the repopulation of normal stem cells

  • The use of concomitant chemotherapy may significantly prolong and worsen acute reactions


Late or chronic side effects

  • Probably represents cell loss from microvascular injury (perhaps secondary to endothelial apoptosis) and organ or tissue atrophy. Inflammation is rarely seen unless infection becomes superimposed

  • Occur months or years after RT

  • Generally progress slowly and are usually irreversible

  • Can result in permanent undesirable effects of RT without sacrificing tumor control

Morbidity Scoring

Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)1

Tolerance Dose (TD)

  • Refers to the normal tissue tolerance of each organ to radiation

  • TD 5/5 is the dose that results in a 5% rate of major complications within 5 years after treatment (presumes that RT is given with the conventional fraction size of 1.8–2 Gy/day). TD 50/5 is the dose that results in a 50% rate of major complications within 5 years after treatment

  • Attempts have been made to define the TD 5/5 for each organ2

  • The defined TD 5/5 should be used only as a guideline and not as an absolute. In the current era of combining chemotherapy and radiation or using altered fractionation schedules, adjustments in the tolerance doses are necessary

Radiation Complications

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Radiation Complications

Normal Tissue Tolerance to Therapeutic Irradiation

Organ Selected End Point TD 5/5 Volume TD 50/5 Volume
1/3 2/3 3/3 1/3 2/3...

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