Chapter 081. Principles of Cancer Treatment (Part 5)

Although radiation can interfere with many cellular processes, many experts feel that a cell must undergo a double-strand DNA break from radiation in order to be killed. The factors that influence tumor cell killing include the D0 of the tumor (the dose required to deliver an average of one lethal hit to all the cells in a population), the Dq of the tumor (the threshold dose—a measure of the cells ability to repair sublethal damage), hypoxia, tumor mass, growth fraction, and cell cycle time and phase (cells in late G1 and S are more resistant). Rate of clinical response...
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Chapter 081. Principles of Cancer Treatment (Part 5) Chapter 081. Principles of Cancer Treatment (Part 5) Although radiation can interfere with many cellular processes, manyexperts feel that a cell must undergo a double-strand DNA break from radiation inorder to be killed. The factors that influence tumor cell killing include the D0 ofthe tumor (the dose required to deliver an average of one lethal hit to all the cellsin a population), the Dq of the tumor (the threshold dose—a measure of the cellsability to repair sublethal damage), hypoxia, tumor mass, growth fraction, and cellcycle time and phase (cells in late G1 and S are more resistant). Rate of clinicalresponse is not predictive; some cells do not die after radiation exposure until theyattempt to replicate. Therapeutic radiation is delivered in three ways: (1) teletherapy, withbeams of radiation generated at a distance and aimed at the tumor within thepatient; (2) brachytherapy, with encapsulated sources of radiation implanteddirectly into or adjacent to tumor tissues; and (3) systemic therapy, withradionuclides targeted in some fashion to a site of tumor. Teletherapy is the mostcommonly used form of radiation therapy. Radiation from any source decreases in intensity as a function of the squareof the distance from the source (inverse square law). Thus, if the radiation sourceis 5 cm above the skin surface and the tumor is 5 cm below the skin surface, theintensity of radiation in the tumor will be 52/102, or 25% of the intensity at theskin. By contrast, if the radiation source is moved to 100 cm from the patient, theintensity of radiation in the tumor will be 1002/1052, or 91% of the intensity at theskin. Teletherapy maintains intensity over a larger volume of target tissue byincreasing the source-to-surface distance. In brachytherapy, the source-to-surfacedistance is small; thus, the effective treatment volume is small. X-rays and gamma rays are the forms of radiation most commonly used totreat cancer. They are both electromagnetic, nonparticulate waves that cause theejection of an orbital electron when absorbed. This orbital electron ejection iscalled ionization. X-rays are generated by linear accelerators; gamma rays aregenerated from decay of atomic nuclei in radioisotopes such as cobalt and radium.These waves behave biologically as packets of energy, called photons. Particulateforms of radiation are also used in certain circumstances. Electron beams have avery low tissue penetrance and are used to treat skin conditions such as mycosisfungoides. Neutron beams may be somewhat more effective than x-rays in treatingsalivary gland tumors. However, aside from these specialized uses, particulateforms of radiation such as neutrons, protons, and negative mesons, which shoulddo more tissue damage because of their higher linear energy transfer and be lessdependent on oxygen, have not yet found wide applicability to cancer treatment. A number of parameters influence the damage done to tissue by radiation.Hypoxic cells are relatively resistant. Nondividing cells are more resistant thandividing cells. In addition to these biologic parameters, physical parameters of theradiation are also crucial. The energy of the radiation determines its ability topenetrate tissue. Low-energy orthovoltage beams (150–400 kV) scatter when theystrike the body, much like light diffuses when it strikes particles in the air. Suchbeams result in more damage to adjacent normal tissues and less radiationdelivered to the tumor. Megavoltage radiation (>1 MeV) has very low lateralscatter; this produces a skin-sparing effect, more homogeneous distribution of theradiation energy, and greater deposit of the energy in the tumor, or target volume.The tissues that the beam passes through to get to the tumor are called the transitvolume. The maximum dose in the target volume is often the cause ofcomplications to tissues in the transit volume, and the minimum dose in the targetvolume influences the likelihood of tumor recurrence. Dose homogeneity in thetarget volume is the goal. Radiation is quantitated on the basis of the amount of radiation absorbed inthe patient; it is not based on the amount of radiation generated by the machine.The rad (radiation absorbed dose) is defined as 100 erg of energy per gram oftissue. The International System (SI) unit for rad is the Gray (Gy); 1 Gy = 100 rad.Radiation dose is measured by placing detectors at the body surface or calculatingthe dose based on radiating phantoms that resemble human form and substance.Radiation dose has three determinants: total absorbed dose, number of fractions,and time. A frequent error is to omit the number of fractions and the duration oftreatment. This is analogou ...