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Radiation Therapy for Cancer

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  • 239
    Radiation Therapy for Cancer
    David A. Jaffray and Mary K. Gospodarowicz
    More than 14 million new cases of cancer are diagnosed
    globally each year; radiation therapy (RT) has the
    potential to improve the rates of cure of 3.5 million
    people and provide palliative relief for an additional
    3.5 million people. These conservative estimates are
    based on the fact that approximately 50 percent of all
    cancer patients can benefit from RT in the management
    of their disease (Barton, Frommer, and Shafiq 2006;
    Barton and others 2014; Tyldesley and others 2011);
    of these, approximately half present early enough to
    pursue curative intent.
    Soon after Roentgens discovery of X-rays in 1895,
    ionizing radiation was applied to the treatment of can-
    cer, with remarkable results. Carefully controlled doses
    of ionizing radiation induce damage to the DNA in cells,
    with preferential effects on cancer cells compared with
    normal tissues, providing treatment benefits in most
    types of cancer and saving lives.
    RT is now recognized as an essential element of an
    effective cancer care program throughout the world,
    regardless of countries’ economic status. RT is used
    to cure cancers that are localized; it also can provide
    local control—complete response with no recurrence
    in the treated area—or symptom relief in cancers that
    are locally advanced or disseminated (Gunderson and
    Tepper 2012). It is frequently used in combination with
    surgery, either preoperatively or postoperatively, as well
    as in combination with systemic chemotherapy before,
    during, or subsequent to the course of RT (Barton and
    others 2014).
    Because radiation affects normal tissues and tumors,
    achieving an acceptable therapeutic ratio—defined as
    the probability of tumor control versus the probability
    of unacceptable toxicity—requires that the radiation
    dose be delivered within very tightly controlled toler-
    ances with less than 5 percent deviation. This controlled
    production and precise application of radiation requires
    specialized equipment that is maintained and operated
    by a team of trained personnel. The team includes,
    at a minimum, radiation oncologists to prescribe the
    appropriate dose, medical physicists to ensure accurate
    dose delivery, and radiation technologists to operate the
    equipment and guide patients through the radiation
    process. Radiation oncologists work within multidisci-
    plinary teams with medical and surgical oncologists to
    coordinate a multidisciplinary approach to the manage-
    ment of cancer. A comprehensive cancer center provides
    the full scope of RT services, ranging from externally
    applied beams of X-rays to the placement of radia-
    tion-emitting sources within tumors (see chapter 11 in
    this volume [Gospodarowicz and others 2015]).
    RT is one of the more cost-effective cancer treat-
    ment modalities, despite the need for substantial capital
    investment in the facilities and equipment. Concerns
    about the initial investment, however, have resulted in
    severely limited access in most low- and middle-income
    countries (LMICs). Increasing the supply of RT services
    is critical to expanding effective cancer treatment in
    Corresponding author: David A. Jaffray, University of Toronto, Princess Margaret Cancer Centre, and TECHNA Institute, David.Jaffray@rmp.uhn.on.ca.
  • 240 Cancer
    these settings and improving equity in access (Abdel-
    Wahab and others 2013; Fisher and others 2014; Goss
    and others 2013; Jaffray and Gospodarowicz 2014;
    Rodin and others 2014; Rosenblatt and others 2013).
    RT is an essential element of curative treatment of can-
    cers of the breast, prostate, cervix, head and neck, lung,
    and brain, as well as sarcomas. The first four cancers are
    common in LMICs (Barton and others 2014; Delaney,
    Jacob, and Barton 2005b; Engstrom and others 2010;
    Gregoire and others 2010; Petrelli and others 2014;
    Pfister and others 2013; Ramos, Benavente, and Giralt
    2010; Souchon and others 2009; Tyldesley and others
    2011). RT is also used extensively in the management
    of prostate cancer (Delaney, Jacob, and Barton 2005a;
    Tyldesley and others 2011).
    Patients with hematologic malignancies are primar-
    ily treated with chemotherapy, but they also access RT
    resources (Barton and others 2014). Total body irradia-
    tion is used in the treatment of leukemia in the context
    of bone marrow transplantation. Localized RT is applied
    in many lymphomas to optimize local disease control
    and cure; palliative RT is extremely useful in multiple
    myeloma and lymphomas. RT is increasingly used to
    control selected metastases. In short, RT both saves lives
    and alleviates suffering associated with cancer.
    Radiation Therapy Alone
    RT as the sole therapy is used in the treatment of local-
    ized tumors, such as early-stage cancer of the larynx or
    prostate; non-melanoma skin cancer; head and neck
    cancers; and radiosensitive tumor types, such as semi-
    noma and lymphomas (Hoppe and others 2012; Motzer
    and others 2009). In more advanced disease stages, RT
    is used before, during, or after surgery and is frequently
    combined with chemotherapy, either as concurrent or
    adjuvant treatment.
    Prior to the development of sophisticated comput-
    erized treatment planning systems, RT was planned
    using clinical information and conventional X-rays
    (2D RT) for field placement verification. This approach
    resulted in the use of large radiotherapy fields that
    assured coverage of the tumor, but also resulted in
    limiting toxicity. With the introduction of computerized
    tomography (CT) scanners and computerized treatment
    planning, fields were shaped (3D conformal radiation
    therapy, 3D CRT) to correspond to the tumors; the use
    of smaller fields resulted in less toxicity and the ability
    to escalate the radiation dose, with resulting improved
    outcomes and reduced toxicity. Now 3D CRT is the
    standard approach in most countries. However, in some
    low-income countries, the introduction of basic 2D
    radiotherapy would still save many lives and reduce suf-
    fering in thousands of patients with advanced cancers.
    The use of high-dose RT has been limited by
    the dose delivered to adjacent normal tissues, espe-
    cially those areas with limited radiation tolerance,
    called critical normal structures. Continued progress
    in computerization of RT planning and delivery allows
    shaping the radiation field to deposit higher doses to
    tumors and further sparing the surrounding normal
    tissues. These newer techniques—intensity modulated
    radiation therapy (IMRT) and stereotactic RT—allow
    a therapeutic dose of RT to be delivered in a few high-
    dose treatments and result in a higher probability of
    tumor eradication; they have been successfully applied
    in the management of brain metastasis and lung,
    bone, and paraspinal tumors. IMRT is being gradually
    introduced in many centers and is the preferred treat-
    ment for cancers of the prostate, as well as, head and
    neck, where it has been shown to improve outcomes
    Concurrent Chemotherapy and Radiation Therapy
    The use of concurrent chemotherapy and RT has sig-
    nificantly improved tumor eradication and survival in
    several cancers. It may improve local control, result in
    organ preservation, and eradicate distant microscopic
    metastases. This combination therapy has proven ben-
    eficial in treating cancers of the lung, cervix, head and
    neck, vulva, and anal canal (Benson and others 2012;
    Chen and others 2013; Glynne-Jones and Renehan 2012;
    Gregoire and others 2010; Koh and others 2013; Petrelli
    and others 2014).
    Radiation Therapy as Adjuvant Treatment
    RT is commonly used as adjuvant treatment following
    surgery, especially in the case of incomplete resection.
    Postoperative radiation is commonly used in cancers
    of the head and neck, rectum, breast, and lung, as well
    as soft tissue sarcomas (Gunderson and Tepper 2012).
    RT is also used after chemotherapy as the mainstay of
    treatment when chemotherapy alone was not expected
    to result in cure, such as for locally advanced breast
    cancer or bladder cancer, or as adjuvant treatment to
    potentially curative chemotherapy, such as for Hodgkin
    and non-Hodgkin lymphomas.
  • Radiation Therapy for Cancer 241
    Radiation Therapy in Metastatic Disease
    RT is beneficial in providing palliation to patients with
    metastatic disease. It is highly effective in controlling
    bleeding and pain, as well as the symptoms result-
    ing from compression of the nerves, spinal cord, or
    airways. The use of RT for pain relief is particularly
    valuable; a single moderate dose (8–10 Gy) achieves
    significant pain relief in 60–80 percent of patients.
    This benefit is of particular importance in LMICs,
    where many patients present with advanced and
    metastatic disease.
    RT is delivered in three ways:
    External beam radiation therapy: applied externally
    through directed beams of radiation to treat the can-
    cer deep within the body.
    Brachytherapy: applied through the insertion of
    radiation- emitting sources directly within the tumor
    or adjacent body cavity.
    Radioisotope therapy: applied through the systemic
    injection of a radioisotope that has been designed to
    target disease.
    Externally applied radiation beams can be produced
    by several approaches: radioactive sources, such as
    cobalt-60, that emit gamma rays; high-energy X-rays
    or photons produced by linear accelerators; or particle
    beams—electrons, protons, or heavier ions— accelerated
    by other types of accelerators. These machines are
    equipped with accessories that are able to shape dynam-
    ically the radiation beam according to beam direction,
    as well as onboard imaging devices that can verify the
    accuracy of treatment delivery. Linear accelerators are
    currently the backbone of external beam RT; multiple
    companies manufacture the technologies, offering a
    range of high-energy X-rays (4–25 MV) to enable treat-
    ment of deep-seated tumors.
    Brachytherapy involves either temporarily or per-
    manently placing radiation-emitting sources directly
    within tissues or body cavities. Permanent sources
    decay rapidly, depositing the dose and remaining in
    the body; temporary placement uses higher-activity
    sources that are electromechanically guided to tumors
    within preplaced interstitial or intracavitary catheters.
    The source and applicators are removed after delivery
    of the prescribed dose of radiation. These removable
    radiation sources can provide either low-dose rate bra-
    chytherapy, where the source remains in the tissues for
    several days, or high-dose rate brachytherapy, where the
    single dose of radiation is delivered within minutes.
    Radioisotope therapy may be applied in the radio-
    therapy department or in the nuclear medicine depart-
    ment. The most common application of radioisotope
    therapy is in the treatment of thyroid cancer using
    radioactive iodine or in the palliation of pain from bone
    metastasis using a radioactive isotope of strontium.
    Less common indications employ a conjugated radio-
    isotope such as lutetium (
    Lu) DOTA-TATE to target
    somatostatin -expressing neuroendocrine tumors.
    RT is delivered in a specially designed facility that
    contains specialized equipment for imaging, treatment
    planning, and radiation delivery. Modern RT depart-
    ments are designed to optimize patient flow through the
    process and contain the following elements:
    • Waiting areas
    • Examination rooms
    Imaging suites with simulators/CT-simulators
    Computer planning workrooms
    Shielded treatment rooms for linear accelerators or
    Co treatment units
    Shielded high-dose rate brachytherapy suites.
    Additional support space is required for a physics
    testing laboratory, equipment storage, and dedicated
    environmentally controlled computer server rooms.
    External beam RT is delivered using machines that
    produce high-energy X-ray or electron beams. The
    two main types of photon beams are
    Co machines
    or X-ray-generating linear accelerators. Cobalt units
    contain radioactive cobalt sources in the head of the
    unit that emit photons with a mean energy of 1.25 MeV.
    The source is constantly emitting and requires con-
    stant radiation protection; it decays gradually and
    requires replacement every three to five years. Linear
    accelerators use electric power to generate an electron
    beam that is accelerated to produce a high-energy
    photon beam. Linear accelerators require a stable
    power supply for reliable operation. Both units have
    collimators and filters to shape the radiation beam,
    including multileaf collimators that allow motorized
    shaping and/or modulation of the beam shape and
    intensity during treatment delivery, thereby produc-
    ing more conformal irradiation of the target tissues
    while minimizing normal tissue exposure. In the past
    10 years, X-ray and CT imaging capabilities have been

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Radiation Therapy for Cancer

Recognizes the essential role of radiation therapy (RT) in cancer treatment as a cost-effective modality despite the substantial outlay in facilities and equipment. RT can be used as a sole therapy, in conjunction with chemotherapy, following surgery, or in palliation. Three delivery methods – external beam radiation therapy, brachytherapy, and radioisotope therapy – are the most common, offered in specially designed facilities by specially trained teams of professionals. In cancer centers, RT departments collaborate with pathology, imagining, surgery, and palliative care groups. An access gap exists between high-income countries and low- and middle-income countries, with special attention needed for medical education, regulatory structure, and infrastructure in less developed countries. The International Atomic Energy Agency (IAEA) has brought attention to this inequity and organized the Programme of Action for Cancer Therapy to assess country readiness to develop RT facilities in light of resources available for cancer control. Planning has improved access in Brazil, Ireland, Canada, Kenya, and Poland.

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