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BRAIN TUMORS: CANCER MEDICINE AND TARGETED THERAPY JASSIN M. JOURIA, MD DR. JASSIN M. JOURIA IS A MEDICAL DOCTOR, PROFESSOR OF ACADEMIC MEDICINE, AND MEDICAL AUTHOR. HE GRADUATED FROM ROSS UNIVERSITY SCHOOL OF MEDICINE AND HAS COMPLETED HIS CLINICAL CLERKSHIP TRAINING IN VARIOUS TEACHING HOSPITALS THROUGHOUT NEW YORK, INCLUDING KING’S COUNTY HOSPITAL CENTER AND BROOKDALE MEDICAL CENTER, AMONG OTHERS. DR. JOURIA HAS PASSED ALL USMLE MEDICAL BOARD EXAMS, AND HAS SERVED AS A TEST PREP TUTOR AND INSTRUCTOR FOR KAPLAN. HE HAS DEVELOPED SEVERAL MEDICAL COURSES AND CURRICULA FOR A VARIETY OF EDUCATIONAL INSTITUTIONS. DR. JOURIA HAS ALSO SERVED ON MULTIPLE LEVELS IN THE ACADEMIC FIELD INCLUDING FACULTY MEMBER AND DEPARTMENT CHAIR. DR. JOURIA CONTINUES TO SERVES AS A SUBJECT MATTER EXPERT FOR SEVERAL CONTINUING EDUCATION ORGANIZATIONS COVERING MULTIPLE BASIC MEDICAL SCIENCES. HE HAS ALSO DEVELOPED SEVERAL CONTINUING MEDICAL EDUCATION COURSES COVERING VARIOUS TOPICS IN CLINICAL MEDICINE. RECENTLY, DR. JOURIA HAS BEEN CONTRACTED BY THE UNIVERSITY OF MIAMI/JACKSON MEMORIAL HOSPITAL’S DEPARTMENT OF SURGERY TO DEVELOP AN E-MODULE TRAINING SERIES FOR TRAUMA PATIENT MANAGEMENT. DR. JOURIA IS CURRENTLY AUTHORING AN ACADEMIC TEXTBOOK ON HUMAN ANATOMY & PHYSIOLOGY. Abstract The field of brain tumor research, diagnosis, and treatment is rapidly evolving. Over 120 types of brain tumors have been identified to date, and that number continues to increase. As the brain tumor research grows, so does the ability to provide improved diagnostic procedures and targeted therapies. It is essential that health clinicians understand current medical treatment options in order to educate patients and to develop a treatment plan that has a positive outcome while respecting the patient's needs and desires. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1 Policy Statement This activity has been planned and implemented in accordance with the policies of NurseCe4Less.com and the continuing nursing education requirements of the American Nurses Credentialing Center's Commission on Accreditation for registered nurses. It is the policy of NurseCe4Less.com to ensure objectivity, transparency, and best practice in clinical education for all continuing nursing education (CNE) activities. Continuing Education Credit Designation This educational activity is credited for 4.5 hours. Nurses may only claim credit commensurate with the credit awarded for completion of this course activity. Pharmacy content is 1 hour. Statement of Learning Need Health clinicians need to know the treatment options for benign and malignant brain tumors, as well as the side effects the treatments may cause. The clinician, with the input of the patient, must be able to understand the potential benefits of treatment, weighed against the potential side effects. Course Purpose To provide health clinicians with knowledge of the current treatment options for brain tumors and to assist clinicians to offer optimal health care for a brain tumor patient. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 2 Target Audience Advanced Practice Registered Nurses and Registered Nurses (Interdisciplinary Health Team Members, including Vocational Nurses and Medical Assistants may obtain a Certificate of Completion) Course Author & Planning Team Conflict of Interest Disclosures Jassin M. Jouria, MD, William S. Cook, PhD, Douglas Lawrence, MA, Susan DePasquale, MSN, FPMHNP-BC – all have no disclosures Acknowledgement of Commercial Support There is no commercial support for this course. Please take time to complete a self-assessment of knowledge, on page 4, sample questions before reading the article. Opportunity to complete a self-assessment of knowledge learned will be provided at the end of the course. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 3 1. Over ________ types of brain tumors have been identified to date, and that number continues to increase. a. b. c. d. 30 four 60 120 2. The choice of antiepileptic drugs is challenging for patients with brain tumor-related epilepsy (BTRE) because BTRE a. b. c. d. is untreatable. is often drug-resistant. requires surgery as the first line of treatment. is caused by the presence of a tumor. 3. In brain tumor patients, the presence of _________ is considered the most important risk factor for long-term disability. a. b. c. d. a cerebral edema depression a comorbidity epilepsy 4. Among the recently marketed drugs, ___________ has demonstrated promising results and should be considered a possible treatment option. a. b. c. d. lacosamide carbamazepine phenobarbital phenytoin 5. True or False: In patients with a brain tumor, seizures are the onset symptom in 20-40% of patients, while a further 20-45% of patients will present seizures during the course of the disease. a. True b. False nursece4less.com nursece4less.com nursece4less.com nursece4less.com 4 Introduction A brain tumor is an abnormal growth of tissue in the brain or central spine that can disrupt proper brain function. Physicians refer to a tumor based on where the tumor cells originated, and whether they are cancerous (malignant) or not cancerous (benign). Some are primary brain tumors, which start in the brain. Others are metastatic, and they start somewhere else in the body and move to the brain. Brain and spinal cord tumors are different in every individual. They form in different areas, develop from different cell types, and may have different treatment options. As the information available about brain tumors has grown, so has the screening/diagnostic methods, and specific targeted therapies to provide patients with optimal health outcomes. Health clinicians need to understand the medical treatment options for brain tumor patients in order to communicate options to patients and their families while respecting the patient's needs and preferences. Targeted Therapy And Treatment Options Since there are over 120 types of brain tumors identified to date, and those numbers continue to increase, the diagnosis of brain tumors has developed to include performance of a neurologic exam as well as diagnostic testing that includes an magnetic resonance imaging (MRI), computed tomography (CT) scan, and biopsy. Treatment options include watchful waiting, surgery, radiation therapy, chemotherapy, and targeted therapy. Targeted therapy uses substances that attack cancer cells without harming normal cells. Many people typically receive a combination of treatments. The field of brain tumor research, diagnosis, and treatment may include any of the following medication and procedural approaches to slow cancer growth and prevent spread. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 5 Antiseizure or Antiepileptic Drugs In patients with a brain tumor (BT), seizures are the onset symptom in 20-40% of patients, while an additional 20-45% of patients will present them during the course of the disease. These patients present a complex therapeutic profile and require a unique and multidisciplinary approach. The choice of antiepileptic drugs is challenging for this particular patient population because brain tumorrelated epilepsy (BTRE) is often drug-resistant. It also has a major impact on the quality of a BTRE patient’s life and weighs heavily on public health expenditures.1 In brain tumor patients, the presence of epilepsy is considered the most important risk factor for long-term disability. For this reason, the problem of the proper administration of medications and their potential side effects is of great importance, because good seizure control can significantly improve the patient’s psychological and relational sphere.2 In these patients, new generation drugs such as gabapentin (GPN), lacosamide (LCM), levetiracetam (LEV), oxcarbazepine (OXC), pregabalin (PGB), topiramate (TPM), and zonisamide (ZNS) are preferred because they have fewer drug interactions and cause fewer side effects. Among the recently marketed drugs, lacosamide has demonstrated promising results and should be considered a possible treatment option.3 It is necessary to develop a customized treatment plan for each individual patient with BTRE. This requires a vision of patient management concerned not only with medical therapies (pharmacological, surgical, radiological, etc.) but also with emotional nursece4less.com nursece4less.com nursece4less.com nursece4less.com 6 and psychological support for the individual as well as his or her family throughout all stages of the illness.4 The potential consequences of using the older generation of antiepileptic drugs (carbamazepine (CBZ), phenobarbital (PB), and phenytoin (PHT)) must be seen not only in the context of their potential to cause serious side effects but must also be seen in terms of their possible contribution to a reduction in the patient’s life expectancy, due to their negative impact on systemic therapies. In addition, systemic treatments can also interfere with the metabolism of these older drugs, thus reducing their plasma levels and consequently the drug’s efficacy in BT patients. The newer antiepileptic drugs, such as lamotrigine, levetiracetam, oxcarbazepine, topiramate and the older antiepileptic drugs, valproic acid (VPA), can be considered first choice therapies in monotherapy, for all of the reasons previously discussed. These same antiepileptic drugs can be considered as add-on, in addition to lacosamide, pregabalin, and zonisamide.5,6 The therapeutic plan should take into consideration the following: Whether or not a specific anticancer therapy is needed. Whether or not a rapid titration is needed (i.e., in patients with a low life-expectancy, as is the case with brain metastases). For some patients, antiepileptic drugs may have a secondary, “positive” effect; for example, pregabalin or topiramate may have a sedative effect in patients who are agitated, while oxcarbazepine or lamotrigine will elevate mood in depressed patients.7 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 7 In addition, the team of healthcare professionals should create a relationship with brain tumor-related epilepsy patients that focuses on accompanying them and their family throughout the illness, offering not only medical support, but also the opportunity for patients to be heard and to be supported during medical and personal challenges and/or difficulties. Taking care of the patient with BTRE means listening and understanding the patent’s choices as well as respecting his or her priorities. Health clinicians need to appreciate the fact that “taking care of” these patients does not mean “curing” as much as it means recognizing and responding to the needs of each unique individual.1,8 Steroids Steroids are naturally occurring substances. In brain tumor treatment, steroids are used to reduce the brain swelling, or cerebral edema, sometimes caused by the tumor or its treatment. The steroids given to brain tumor patients are corticosteroids – hormones produced by the adrenal glands. They are not the same as the anabolic steroids used by athletes to build muscle.9 Dexamethasone and prednisone are the most commonly used corticosteroid drugs. These steroids can temporarily improve neurological symptoms by reducing brain swelling but in most cases do not directly treat the tumor. Because steroids are hormones, their long-term use requires close monitoring. Steroids may be prescribed when a brain mass is seen on an MRI or CT scan of the brain, around the time of surgery or radiation, or sometimes with chemotherapy. Steroids are used for short-term symptom control although they may occasionally be continued for a period of weeks or months. Steroids nursece4less.com nursece4less.com nursece4less.com nursece4less.com 8 can also be used for other reasons. They can improve appetite, prevent nausea and vomiting from chemotherapy, reduce pain and prevent allergic reactions to some chemotherapies.10-12 In the case of most brain tumors, steroids are not prescribed to eliminate cancer cells. One exception is primary central nervous system lymphoma (PCNSL), which is a lymphoma involving the brain or spinal cord. If this type of tumor is suspected, steroids are not usually used until after the diagnosis is confirmed by biopsy or removal of the tumor. Please note that even in lymphoma steroids are not typically a long-term cure for this tumor.13 Steroids are usually administered intravenously (IV) or by mouth (orally). It may take 24–48 hours before the patient will begin to see the effects of the medication, but the change is often remarkable. The dose used is dependent on how much swelling is seen on the MRI or CT scan of the brain. To protect the stomach, patients should take their steroids with food or milk. An additional medication may also be prescribed to further protect the stomach. As with all medication, the goal is to use the lowest, most effective dose. This may mean the dose is adjusted up or down to find the best dose for the patient. The goal for steroid use is to administer the lowest dose to control symptoms or to obtain desired CT or MRI changes.14 When the patient no longer requires steroids, he or she will be given instructions to slowly taper and stop the drug. Patients should not abruptly stop taking their steroids. A gradual reduction of steroid dose allows the body to begin producing its own steroids again. This gradual tapering avoids adrenal crisis, which is caused by insufficient levels of nursece4less.com nursece4less.com nursece4less.com nursece4less.com 9 the hormone cortisol. Lowering steroid levels too quickly can also cause a rebound increase in brain swelling and return of symptoms and sometimes joint pain.11 Side Effects Steroids can cause a wide range of unwanted effects. The most common side effects include increased appetite, weight gain, increased blood sugar levels (especially in patients who have diabetes), gastrointestinal problems (i.e., stomach ulcers), frequent urination, insomnia and mood changes such as irritability or mania, muscle weakness, susceptibility to infections like pneumonia, thinning of the skin, and acne. Steroids can interact with other medications, either increasing or decreasing the levels in the patient’s blood, which can alter their effectiveness or increase their side effects. Other more serious side effects can occur, although they are less common. The benefits of steroid use almost always outweigh their potential side effects when they are prescribed.9,10 Radiation Therapy Radiation is a common treatment method for individuals who are able to tolerate it. This treatment is delivered using high-energy particles or waves that disrupt the cancer. These particles create small breaks in the DNA that is inside the cells, which prevent the cancer cells from dividing and growing.15 The following are common delivery methods16 for radiation: X-rays Gamma rays Electron beams Protons nursece4less.com nursece4less.com nursece4less.com nursece4less.com 10 Radiation is especially favorable for cancer that is located in one region of the body as it can be delivered as a localized treatment. It does not expose the entire body to treatment as happens with medication, delivering treatment instead to one specific region.17 Radiation therapy can be used independently to treat cancer, or it can be used in conjunction with another method of treatment. In many instances, radiation will be combined with surgery or chemotherapy.18 The type of radiation therapy used to treat the patient depends on many factors, including:15 The type of cancer. The size of the cancer. The cancer’s location in the body. How close the cancer is to normal tissues that are sensitive to radiation. How far into the body the radiation needs to travel. The patient’s general health and medical history. Whether the patient will have other types of cancer treatment. Other factors, such as the patient’s age and other medical conditions. Types of Radiation There are three primary types of radiation therapy.19 They are: External-beam Radiation Therapy Internal radiation therapy Systemic radiation therapy nursece4less.com nursece4less.com nursece4less.com nursece4less.com 11 External-beam Radiation Therapy External-beam radiation therapy is most often delivered in the form of photon beams (either x-rays or gamma rays). A photon is the basic unit of light and other forms of electromagnetic radiation. It can be thought of as a bundle of energy. The amount of energy in a photon can vary. For example, the photons in gamma rays have the highest energy, followed by the photons in x-rays. Patients usually receive external-beam radiation therapy in daily treatment sessions over the course of several weeks. The number of treatment sessions depends on many factors, including the total radiation dose that will be given. Intensitymodulated radiation therapy (IMRT) IMRT uses hundreds of tiny radiation beam-shaping devices, called collimators, to deliver a single dose of radiation. The collimators can be stationary or can move during treatment, allowing the intensity of the radiation beams to change during treatment sessions. This kind of dose modulation allows different areas of a tumor or nearby tissues to receive different doses of radiation. Unlike other types of radiation therapy, IMRT is planned in reverse (called inverse treatment planning). In inverse treatment planning, the radiation oncologist chooses the radiation doses to different areas of the tumor and surrounding tissue, and then a high-powered computer program calculates the required number of beams and angles of the radiation treatment. In contrast, during traditional (forward) treatment planning, the radiation oncologist chooses the number and angles of the radiation beams in advance and computers calculate how much dose will be delivered from each of the planned beams. The goal of IMRT is to increase the radiation dose to the areas that need it and reduce radiation exposure to specific sensitive areas of surrounding normal tissue. Compared with three-dimensional conformal radiotherapy (3D-CRT), IMRT can reduce the risk of some side effects, such as damage to the salivary glands (which can cause dry mouth, or xerostomia), when the head and neck are treated with radiation therapy. However, with IMRT, a larger volume of normal tissue overall is exposed to radiation. Whether IMRT leads to improved control of tumor growth and better survival compared with 3D-CRT is not yet known. Image-guided radiation therapy (IGRT) In IGRT, repeated imaging scans (CT, MRI, or PET) are performed during treatment. Imaging scans are processed by computers, identifying changes in a tumor’s size and location due to treatment and allowing patient positioning or planned radiation dose adjusting during treatment. Repeated imaging can increase the accuracy of radiation treatment and may allow reductions in the planned volume of tissue to be treated, thereby decreasing the total radiation dose to normal tissue. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 12 Tomotherapy Tomotherapy is a type of image-guided IMRT. A tomotherapy machine is a hybrid between a CT imaging scanner and an external-beam radiation therapy machine. The part of the tomotherapy machine that delivers radiation for both imaging and treatment can rotate completely around the patient in the same manner as a normal CT scanner. Tomotherapy machines can capture CT images of the patient’s tumor immediately before treatment sessions, to allow for very precise tumor targeting and sparing of normal tissue. Like standard IMRT, tomotherapy may be better than 3DCRT at sparing normal tissue from high radiation doses. However, clinical trials comparing 3D-CRT with tomotherapy have not been conducted. Stereotactic radiosurgery Stereotactic radiosurgery (SRS) can deliver one or more high doses of radiation to a small tumor. SRS uses extremely accurate image-guided tumor targeting and patient positioning. Therefore, a high dose of radiation can be given without excess damage to normal tissue. SRS can be used to treat only small tumors with welldefined edges. It is most commonly used in the treatment of brain or spinal tumors and brain metastases from other cancer types. For the treatment of some brain metastases, patients may receive radiation therapy to the entire brain (called whole-brain radiation therapy) in addition to SRS. SRS requires the use of a head frame or other device to immobilize the patient during treatment to ensure that the high dose of radiation is delivered accurately. Stereotactic body radiation therapy Stereotactic body radiation therapy (SBRT) delivers radiation therapy in fewer sessions, using smaller radiation fields and higher doses than 3D-CRT in most cases. By definition, SBRT treats tumors that lie outside the brain and spinal cord. Because these tumors are more likely to move with the normal motion of the body, and therefore cannot be targeted as accurately as tumors within the brain or spine, SBRT is usually given in more than one dose. SBRT can be used to treat only small, isolated tumors, including cancers in the lung and liver. Proton therapy Proton beams differ from photon beams mainly in the way they deposit energy in living tissue. Whereas photons deposit energy in small packets all along their path through tissue, protons deposit much of their energy at the end of their path (called the Bragg peak) and deposit less energy along the way. In theory, use of protons should reduce the exposure of normal tissue to radiation, possibly allowing the delivery of higher doses of radiation to a tumor. Proton therapy has not yet been compared with standard external-beam radiation therapy in clinical trials. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 13 Other charged particle beams Electron beams are used to irradiate superficial tumors, such as skin cancer or tumors near the surface of the body, but they cannot travel very far through tissue. Therefore, they cannot treat tumors deep within the body. Patients can discuss these different methods of radiation therapy with their physicians to see if any is appropriate for their type of cancer and if it is available in their community or through a clinical trial. Brachytherapy Other Forms of Radiation Internal radiation therapy (brachytherapy) is radiation delivered from radiation sources (radioactive materials) placed inside or on the body. Several brachytherapy techniques are used in cancer treatment. Interstitial brachytherapy uses a radiation source placed within tumor tissue, such as within a prostate tumor. Intracavitary brachytherapy uses a source placed within a surgical cavity or a body cavity, such as the chest cavity, near a tumor. Episcleral brachytherapy, which is used to treat melanoma inside the eye, uses a source that is attached to the eye. In brachytherapy, radioactive isotopes are sealed in tiny pellets or “seeds.” These seeds are placed in patients using delivery devices, such as needles, catheters, or some other type of carrier. As the isotopes decay naturally, they give off radiation that damages nearby cancer cells. If left in place, after a few weeks or months, the isotopes decay completely and no longer give off radiation. The seeds will not cause harm if they are left in the body. Brachytherapy may be able to deliver higher doses of radiation to some cancers than external-beam radiation therapy while causing less damage to normal tissue. Brachytherapy can be given as a low-dose-rate or a highdose-rate treatment: In low-dose-rate treatment, cancer cells receive continuous low-dose radiation from the source over a period of several days. In high-dose-rate treatment, a robotic machine attached to delivery tubes placed inside the body guides one or more radioactive sources into or near a tumor, and then removes the sources at the end of each treatment session. High-dose-rate treatment can be given in one or more treatment sessions. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 14 The placement of brachytherapy sources can be temporary or permanent: For permanent brachytherapy, the sources are surgically sealed within the body and left there, even after all of the radiation has been given off. The remaining material (in which the radioactive isotopes were sealed) does not cause any discomfort or harm to the patient. Permanent brachytherapy is a type of low-dose-rate brachytherapy. For temporary brachytherapy, tubes (catheters) or other carriers are used to deliver the radiation sources, and both the carriers and the radiation sources are removed after treatment. Temporary brachytherapy can be either low-dose-rate or highdose-rate treatment. Physicians can use brachytherapy alone or in addition to external-beam radiation therapy to provide a “boost” of radiation to a tumor while sparing surrounding normal tissue. Systemic radiation therapy In systemic radiation therapy, a patient swallows or receives an injection of a radioactive substance, such as radioactive iodine or a radioactive substance bound to a monoclonal antibody. Radioactive iodine (131I) is a type of systemic radiation therapy commonly used to help treat some types of cancer. In many instances, a monoclonal antibody helps target the radioactive substance to the right place. The antibody joined to the radioactive substance travels through the blood, locating and killing tumor cells. The Food and Drug Administration (FDA) has approved the drug ibritumomab tiuxetan for the treatment of certain types of B-cell non-Hodgkin lymphoma (NHL). The antibody part of this drug recognizes and binds to a protein found on the surface of B lymphocytes. The combination drug regimen of tositumomab and iodine I 131 tositumomab has been approved for the treatment of certain types of NHL. In this regimen, nonradioactive tositumomab antibodies are given to patients first, followed by treatment with tositumomab antibodies that have 131I attached. Tositumomab recognizes and binds to the same protein on B lymphocytes as ibritumomab. The nonradioactive form of the antibody helps protect normal B lymphocytes from being damaged by radiation from 131I. Many other systemic radiation therapy drugs are in clinical trials for different cancer types. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 15 Radiation Side Effects Patients may experience both acute and chronic side effects as a result of radiation treatment. While acute side effects will occur during the course of treatment, chronic side effects may not appear for months or years after treatment has ceased. The prevalence of side effects will depend on the following factors:20 Area of the body being treated Dose given per day Total dose given Patient’s general medical condition Other treatments given at the same time The following is a description of the most common acute and chronic side effects associated with radiation.15 1) Acute: Acute radiation side effects are caused by damage to rapidly dividing normal cells in the area being treated. These effects include skin irritation or damage at regions exposed to the radiation beams. Examples include damage to the salivary glands or hair loss when the head or neck area is treated, or urinary problems when the lower abdomen is treated. Most acute effects disappear after treatment ends, though some (like salivary gland damage) can be permanent. Fatigue is a common side effect of radiation therapy regardless of which part of the body is treated. Nausea with or without vomiting is common when the abdomen is treated and occurs sometimes when the brain is treated. Medications are available to help prevent or treat nausea and vomiting during treatment. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 16 2) Chronic Late side effects of radiation therapy may or may not occur. Depending on the area of the body treated, late side effects can include: Fibrosis (the replacement of normal tissue with scar tissue, leading to restricted movement of the affected area) Damage to the bowels, causing diarrhea and bleeding Memory loss Infertility (inability to have a child) Rarely, a second cancer caused by radiation exposure Second cancers that develop after radiation therapy depend on the part of the body that was treated. For example, girls treated with radiation to the chest for Hodgkin lymphoma have an increased risk of developing breast cancer later in life. In general, the lifetime risk of a second cancer is highest in people treated for cancer as children or adolescents. Chemotherapy Chemotherapy is a common treatment for many cancers. There are approximately one hundred chemotherapy drugs currently in use.21 These drugs can be used individually or in conjunction with other methods of treatment. The specific drugs used will depend on a variety of factors, including the location, severity, and scope of the cancer.22 Chemotherapy drugs vary widely in their chemical composition, how they are taken, their usefulness in treating specific forms of cancer, and their side effects. Although these drugs differ in the ways indicated above, they all work to disrupt the ways in which cancer cells divide and grow. The drugs damage the cells to prevent reproduction. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 17 Unfortunately, chemotherapy drugs also have the same effect on noncancer cells.23 There are a number of delivery methods that can be used with chemotherapy.24 They include: By injection or a “drip” directly into a vein (intravenous chemotherapy) By mouth as tablets or capsules (oral chemotherapy) By other ways, including: by injection into the fluid around the spine and brain (intrathecal chemotherapy); directly into a body cavity, for example the bladder; by injection into muscle or under the skin; directly to the skin as a cream for some skin cancers. Chemotherapy is a useful stand-alone treatment. However, it is often more effective when combined with other therapies such as surgery, radiotherapy, hormonal therapy, or anti-cancer drugs (targeted or biological therapies).25 Chemotherapy can be used in the following ways:26 As a main treatment for cancers, such as lymphomas and leukemia Before surgery or radiotherapy to shrink a cancer (called neoadjuvant chemotherapy) After surgery or radiotherapy to reduce the risk of cancer coming back by treating any remaining cells (called adjuvant chemotherapy) At the same time as radiotherapy to make it work better (called chemoradiation) nursece4less.com nursece4less.com nursece4less.com nursece4less.com 18 To treat cancer that has spread into surrounding tissues (locally advanced) or to other parts of the body. This may cure certain cancers but, more commonly, the aim is to shrink and control a cancer to try to prolong life, and to relieve symptoms. Chemotherapy to relieve symptoms is called palliative chemotherapy. There are 3 possible goals for chemotherapy treatment, which are highlighted below.27 Cure: If possible, chemotherapy is used to cure the cancer, meaning that the cancer disappears and does not return. However, most doctors do not use the word “cure” except as a possibility or intention. When giving treatment that has a chance of curing a person’s cancer, the doctor may describe it as treatment with curative intent. But there are no guarantees, and though cure may be the goal, it does not always work out that way. It often takes many years to know if a person’s cancer is actually cured. Control: If cure is not possible, the goal may be to control the disease — to shrink any cancerous tumors and/or stop the cancer from growing and spreading. This can help someone with cancer feel better and possibly live longer. In many cases, the cancer does not completely go away but is controlled and managed as a chronic disease, much like heart disease or diabetes. In other cases, the cancer may even seem to have gone away for a while, but it’s expected to come back. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 19 Palliation: When the cancer is at an advanced stage, chemotherapy drugs may be used to relieve symptoms caused by the cancer. When the only goal of a certain treatment is to improve the quality of life but not treat the disease itself, it is called palliative treatment or palliation. Sometimes, chemotherapy is the only treatment used. In other cases, chemotherapy may be given along with other treatments. It may be used as adjuvant therapy or neoadjuvant therapy.28 Adjuvant chemotherapy: After surgery to remove the cancer, there may still be some cancer cells left behind that cannot be seen. When drugs are used to kill those unseen cancer cells, it is called adjuvant chemotherapy. Adjuvant treatment can also be given after radiation. Neoadjuvant chemotherapy: Chemotherapy can be given before the main cancer treatment (such as surgery or radiation). Giving chemotherapy first can shrink a large cancerous tumor, making it easier to remove with surgery. Shrinking the tumor may also allow it to be treated more easily with radiation. Neoadjuvant chemotherapy also can kill small deposits of cancer cells that cannot be seen on scans or X-rays. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 20 Administration Methods There are a number of different methods of administering chemotherapy. The specific method used will depend on the type, severity, and scope of the cancer. It will also depend on the health status of the patient and his or her ability to tolerate the treatment. The following table provides a description of each of the primary methods of chemotherapy administration.26 Systemic chemotherapy Systemic chemotherapy involves using drugs to treat the entire body. Treatment is not localized based on the area where the cancer occurs. Drugs used for systemic (total body) chemotherapy can be given in these ways: Oral (PO) — taken by mouth (usually as pills) Intravenous (IV) — infused through a vein Intramuscular (IM) — injected into a muscle Subcutaneous (SQ) — injected under the skin Some chemotherapy drugs are never taken by mouth because the digestive system can’t absorb them or because they irritate the digestive system. Even when a drug is available in an oral form (such as a pill or liquid), this method may not be the best choice. For example, some people with certain symptoms (like severe nausea, vomiting, or diarrhea) cannot swallow liquids or pills; other people may have trouble remembering when or how many pills to take. Still, chemotherapy drugs are powerful treatments, regardless of their form and the way they are administered. The term parenteral is used to describe drugs given into a vein (intravenously or IV), muscle (intramuscularly or IM), or under the skin (subcutaneously or SQ). The IV route is the most common. IM and SQ injections are less often used because many drugs can irritate or even damage the skin and muscle tissue. The IV route gets the drug quickly throughout the body. IV therapy may be given through a catheter placed in a vein in the arm or hand, which is called a “peripheral line.” IV drugs can also be given through a catheter placed into a larger vein in the chest, or neck, which is known as a central venous catheter (CVC) or “central line.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com 21 Central venous catheters (CVCs) or vascular access devices (VADs) may be needed. Central venous catheters are also known as vascular access devices. Some types of catheters are put into the arm (so they are inserted peripherally), but are threaded into a larger vein in the chest. They are used for these reasons: To give several drugs at one time For long-term therapy (to reduce the number of needle sticks) For frequent treatments (using a CVC will not cause as much wear and tear to the veins, potential scarring, and discomfort as numerous IVs that go into the small veins of the arms or hands) For continuous infusion chemotherapy To give drugs that can cause serious damage to skin and muscle tissue if they leak outside of a vein (these drugs are known as vesicants). Delivering these through a CVC provides more reliable access to a vein than a short-term IV, reducing the risk that the drug will leak outside the vein and damage tissues. Regional chemotherapy When there is a need to get high doses of chemotherapy to a specific area of the body, it may be given by a regional method. Regional chemotherapy directs the anti-cancer drugs into the part of the body where the cancer is. The purpose is to get more of the drug to the cancer, while trying to minimize side effects on the whole body. Side effects will often still happen because the drugs can be partly absorbed into the bloodstream and travel throughout the body. Intra-arterial With Intra-arterial chemotherapy, the drug is injected into an artery that goes to a certain area of the body. An intraarterial infusion allows a chemotherapy drug to be given directly to the cancerous tumor through a catheter placed in the artery that supplies blood to the tumor. This method is used to treat disease in an organ such as the liver (isolated hepatic perfusion), or to treat an extremity such as the leg (isolated limb perfusion). The goal is to concentrate the drug in the area of the tumor and decrease systemic side effects. The catheter is attached to an implanted or portable pump. Although this approach sounds like a good idea for better effectiveness and fewer side effects, most studies have not found it to be as useful as expected. This approach is being studied for many types of cancer in clinical trials. Except for these clinical trials, it is rarely available outside of specialized cancer centers. Intracavitary chemotherapy Intracavitary is a broad term used to describe chemotherapy given directly into a body cavity. The chemo drug is given through a catheter placed into one of these areas as described below. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 22 Intravesical Intravesical chemotherapy is often used for early stage bladder cancer. The chemotherapy is usually given weekly for 4 to 12 weeks. For each treatment, a urinary catheter is placed into the bladder to give the drug. The drug is kept in the bladder for about 2 hours and then drained. The urinary catheter is removed after each treatment. Intrapleural Intrapleural chemotherapy is not used very often but may be helpful for some people with mesothelioma (cancer that develops in the lining of the lung), and those with lung or breast cancers that have spread to the pleura (the membrane around the lungs and lining the chest cavity). Intrapleural chemotherapy is given through chest catheters that may be connected to an implantable port. These catheters can be used to give drugs and to drain fluid that can build up in the pleural space when cancer has spread to that area. Intraperitoneal Intraperitoneal chemotherapy has become one of the standard treatments for certain stages of ovarian cancer. It may also be used to treat some recurrent colon cancers, as well as cancers of the appendix or stomach that have spread extensively within the abdomen. Intraperitoneal chemotherapy is given through a Tenckhoff catheter (a catheter specially designed for removing or adding large amounts of fluid from or into the abdominal cavity) or through an implanted port attached to a catheter. Chemotherapy injected into the port travels through the catheter into the abdominal cavity where it’s absorbed into the affected area before entering the bloodstream. This approach can work very well, but it can also have more severe side effects than regular IV chemotherapy. The higher doses that are used, along with more gradual absorption of the drug into the body, may be part of why the side effects may be worse. Intrathecal chemotherapy Intrathecal chemotherapy is given directly into the fluid surrounding the brain and spinal cord (the cerebrospinal fluid or CSF) to reach cancer cells in the fluid and the central nervous system (brain and spinal cord). Most chemotherapy drugs that are put into the bloodstream are unable to cross the barrier between the bloodstream and the central nervous system, called the blood-brain barrier. Intrathecal chemotherapy gets the drug directly to the central nervous system. Intrathecal chemotherapy is given in 1 of 2 ways: The chemotherapy can be given by a lumbar puncture (spinal tap) done daily or weekly. This is when a thin needle is placed between the bones of the lower spine and into the space through which the CSF flows around the spinal cord. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 23 A special device called an Ommaya reservoir can be used. It’s a small, drum-like port, which is placed under the skin of the skull. An attached catheter goes through the skull into a ventricle (a space inside the brain filled with CSF). A special needle is put through the skin and into the port to give the chemotherapy. Chemotherapy is given this way when it is needed to treat cancer cells that have entered the central nervous system (this is called leptomeningeal spread). This is seen most commonly in leukemia’s, but also may happen with some lymphomas and advanced solid tumors like breast and lung cancers. Intrathecal chemotherapy does not help when tumors have already started growing in the brain or spinal cord. Intralesional chemotherapy Intralesional chemotherapy refers to the drug being injected directly into the cancerous tumor. It may be used for tumors that are in or under the skin, and rarely for tumors that are on an organ inside the body. It is only possible when the tumor can be safely reached by a needle, and is most often used when surgery is not an option. Topical chemotherapy In this use, chemotherapy is applied to the skin in the form of a cream or lotion. Most often, it is put onto skin cancers such as the basal cell or squamous cell types. It is also used to treat pre-cancerous growths on the skin. The patient or a family member usually puts on the chemotherapy cream. It is important to understand the schedule, know exactly how to use these potent drugs, and know what kinds of precautions to use. Alternate Chemotherapy Methods There are other ways you might be given chemotherapy, depending on the drugs that are being used and the type of cancer. Injection into a muscle or skin - Some chemotherapy drugs are given by injection into a muscle (intramuscular) of the leg or buttock. This might feel a bit painful or uncomfortable for a short time. Some drugs are given by injection under the skin (subcutaneous) using a very fine needle. Injection into the spinal fluid (intrathecal): In some leukemia’s, lymphomas or some brain tumors cancer cells can pass into the fluid surrounding the brain and spinal cord (cerebrospinal fluid or CSF). Intrathecal chemotherapy can be used to destroy these cancer cells or to try and prevent this from happening. Chemotherapy into a vein or by mouth cannot reach these cancer cells. The doctor numbs an area of skin over the spine with local anesthetic. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 24 After a few minutes they will gently insert a needle between two of the spinal bones into the CSF (called a lumbar puncture). The doctor then injects the chemotherapy through the needle into the CSF. The most common side effect of a lumbar puncture is a headache. To help prevent this, the patient will need to lie flat for a few hours afterwards and drink plenty of fluids. Into a body space (intracavitary): Chemotherapy drugs can be given into a space (cavity) in the body, such as the bladder. This can cause irritation or inflammation in the area the drugs are given but it does not usually cause side effects in other parts of the body. A fine tube (catheter) is usually inserted into the body cavity and chemotherapy is put in through this tube. It may be drained out again after a set period of time. Into the bladder: This may be done to treat early bladder cancer. Liquid chemotherapy drugs are given directly into the bladder through a catheter, which is removed when it is over. Our section on early (superficial) bladder cancer has more information. Into the abdominal cavity (intraperitoneal chemotherapy): This is very occasionally used to treat ovarian cancer and there is more information in our section on cancer of the ovary. It may also be used to treat mesothelioma in the abdomen (peritoneal mesothelioma). Between the two layers of the pleura (tissue that covers the outside of the lungs): Chemotherapy is sometimes put in between the two layers of the pleura to treat cancer cells that have spread there. Into a limb (isolated limb perfusion): Chemotherapy is very occasionally given directly into the blood vessels in a limb. This is to treat a skin cancer called melanoma that has come back. Chemotherapy creams: Chemotherapy creams are used to treat some types of skin cancer. You put the cream on the affected skin in a thin layer and cover the area with a dressing. A specialist nurse or pharmacist will show the patient how to do this and will explain how often they need to apply the cream. Although the cream can irritate the skin in the area or make it sore, it won’t cause side effects in other parts of the body. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 25 Types of Chemotherapy Drugs There are a multitude of chemotherapy drugs that are grouped and categorized based upon a number of factors, including:28 how they work their chemical structure their relationship to another drug Many drugs will belong to more than one of the groups, as some chemotherapy drugs act in more than one way. The following is a list of the different categories of chemotherapy drugs. Alkylating Agents Alkylating agents directly damage DNA to prevent the cancer cell from reproducing. As a class of drugs, these agents are not phase-specific; in other words, they work in all phases of the cell cycle. Alkylating agents are used to treat many different cancers, including leukemia, lymphoma, Hodgkin disease, multiple myeloma, and sarcoma, as well as cancers of the lung, breast, and ovary. Because these drugs damage DNA, they can cause long-term damage to the bone marrow. In rare cases, this can eventually lead to acute leukemia. The risk of leukemia from alkylating agents is “dose-dependent,” meaning that the risk is small with lower doses, but increase as the total amount of the drug used gets higher. The risk of leukemia after getting alkylating agents is highest about 5 to 10 years after treatment. There are different classes of alkylating agents, including: • Nitrogen mustards, such as mechlorethamine (nitrogen mustard), chlorambucil, cyclophosphamide, ifosfamide, and melphalan nursece4less.com nursece4less.com nursece4less.com nursece4less.com 26 • Nitrosoureas, which include streptozocin, carmustine (BCNU), and lomustine • Alkyl sulfonates, busulfan • Triazines, dacarbazine (DTIC) and temozolomide • Ethylenimines, thiotepa and altretamine (hexamethylmelamine) • The platinum drugs (cisplatin, carboplatin, and oxalaplatin), sometimes grouped with alkylating agents because they kill cells in a similar way. These drugs are less likely than the alkylating agents to cause leukemia later on. Antimetabolites Antimetabolites are a class of drugs that interfere with DNA and RNA growth by substituting for the normal building blocks of RNA and DNA. These agents damage cells during the S phase. They are commonly used to treat leukemia, cancers of the breast, ovary, and the intestinal tract, as well as other types of cancer. Examples of antimetabolites include: • 5-fluorouracil (5-FU) • 6-mercaptopurine (6-MP) • Capecitabine • Cladribine • Clofarabine • Cytarabine • Floxuridine • Fludarabine • Gemcitabine • Hydroxyurea • Methotrexate • Pemetrexed nursece4less.com nursece4less.com nursece4less.com nursece4less.com 27 • Pentostatin • Thioguanine Anthracyclines Anthracyclines are anti-tumor antibiotics that interfere with enzymes involved in DNA replication. These drugs work in all phases of the cell cycle. They are widely used for a variety of cancers. A major consideration when giving these drugs is that they can permanently damage the heart if given in high doses. For this reason, lifetime dose limits are often placed on these drugs. Examples of anthracyclines include: • Daunorubicin • Doxorubicin • Epirubicin • Idarubicin Other Anti-tumor Antibiotics Anti-tumor antibiotics that are not anthracyclines include the following. • Actinomycin-D • Bleomycin • Mitomycin-C - Mitoxantrone is an anti-tumor antibiotic that is similar to doxorubicin in many ways, including the potential for damaging the heart. This drug also acts as a topoisomerase II inhibitor (see below), and can lead to treatment-related leukemia. Mitoxantrone is used to treat prostate cancer, breast cancer, lymphoma, and leukemia. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 28 Topoisomerase Inhibitors Topoisomerase inhibitors interfere with enzymes called topoisomerases, which help separate the strands of DNA so they can be copied. They are used to treat certain leukemia’s, as well as lung, ovarian, gastrointestinal, and other cancers. Examples of topoisomerase I inhibitors include topotecan and irinotecan (CPT-11). Examples of topoisomerase II inhibitors include etoposide (VP-16) and teniposide. Mitoxantrone also inhibits topoisomerase II. Treatment with topoisomerase II inhibitors increases the risk of a second cancer — acute myelogenous leukemia (AML). With this type of drug, a secondary leukemia can be seen as early as 2 to 3 years after the drug is given. Mitotic Inhibitors Mitotic inhibitors are often plant alkaloids and other compounds derived from natural products. They can stop mitosis or inhibit enzymes from making proteins needed for cell reproduction. These drugs work during the M phase of the cell cycle but can damage cells in all phases. They are used to treat many different types of cancer including breast, lung, myelomas, lymphomas, and leukemia. These drugs are known for their potential to cause peripheral nerve damage, which can be a dose-limiting side effect. Examples of mitotic inhibitors include: • Taxanes: paclitaxel and docetaxel • Epothilones: ixabepilone • Vinca alkaloids: vinblastine, vincristine, and vinorelbine • Estramustine nursece4less.com nursece4less.com nursece4less.com nursece4less.com 29 Corticosteroids Steroids are natural hormones and hormone-like drugs that are useful in treating some types of cancer (lymphoma, leukemia, and multiple myeloma), as well as other illnesses. When these drugs are used to kill cancer cells or slow their growth, they are considered chemotherapy drugs. Corticosteroids are also commonly used as anti-emetics to help prevent nausea and vomiting caused by chemotherapy. They are used before chemotherapy to help prevent severe allergic reactions (hypersensitivity reactions) as well. When a corticosteroid is used to prevent vomiting or allergic reactions, it is not considered chemotherapy. Examples include prednisone, methylprednisolone, and dexamethasone. Miscellaneous Chemotherapy Drugs Some chemotherapy drugs act in slightly different ways and do not fit well into any of the other categories. Examples include drugs like Lasparaginase, which is an enzyme, and the proteosome inhibitor bortezomib. Other Types of Cancer Drugs Other drugs and biological treatments are used to treat cancer, but are not usually considered chemotherapy. While chemotherapy drugs take advantage of the fact that cancer cells divide rapidly, these other drugs target different properties that set cancer cells apart from normal cells. They often have less serious side effects than those commonly caused by chemotherapy drugs because they are targeted nursece4less.com nursece4less.com nursece4less.com nursece4less.com 30 to work mainly on cancer cells, not normal, healthy cells. Many are used along with chemotherapy. Targeted Therapies As researchers have learned more about the inner workings of cancer cells, they have begun to create new drugs that attack cancer cells more specifically than traditional chemotherapy drugs. Most attack cells with mutant versions of certain genes, or cells that express too many copies of a particular gene. These drugs can be used as part of the main treatment, or they may be used after treatment to maintain remission or decrease the chance of recurrence. Examples of targeted therapies include imatinib, gefitinib, sunitinib and bortezomib. Targeted therapies are a huge research focus and probably many more will be developed in the future. A brief discussion is provided here, but more can be learned about targeted therapies in upcoming literature. Differentiating Agents Differentiating agents act on the cancer cells to make them mature into normal cells. Examples of such drugs include the retinoids, tretinoin and bexarotene, as well as arsenic trioxide. Hormone Therapy Drugs in this category are sex hormones, or hormone-like drugs, that change the action or production of female or male hormones. They are used to slow the growth of breast, prostate, and endometrial (uterine) cancers, which normally grow in response to natural hormones in the body. These cancer treatment hormones do not work in the same ways nursece4less.com nursece4less.com nursece4less.com nursece4less.com 31 as standard chemotherapy drugs, but rather by preventing the cancer cell from using the hormone it needs to grow, or by preventing the body from making the hormones. Examples include the following: • The anti-estrogens: fulvestrant, tamoxifen, and toremifene • Aromatase inhibitors: anastrozole, exemestane, and letrozole • Progestins: megestrol acetate • Estrogens • Anti-androgens: bicalutamide, flutamide, and nilutamide • Gonadotropin-releasing hormone (GnRH), also known as luteinizing hormone-releasing hormone (LHRH) agonists or analogs: leuprolide and goserelin Immunotherapy Some drugs are given to people with cancer to stimulate their natural immune systems to recognize and attack cancer cells. These drugs offer a unique method of treatment, and are often considered to be separate from chemotherapy. Compared with other forms of cancer treatment such as surgery, radiation therapy, or chemotherapy, immunotherapy is still fairly new. There are different types of immunotherapy. Active immunotherapies stimulate the body’s own immune system to fight the disease. Passive immunotherapies do not rely on the body to attack the disease; instead, they use immune system components (such as antibodies) created outside the body. Types of immunotherapies and some examples include:220 • Monoclonal antibody therapy (passive immunotherapies), such as rituximab and alemtuzumab nursece4less.com nursece4less.com nursece4less.com nursece4less.com 32 • Non-specific immunotherapies and adjuvants (other substances or cells that boost the immune response), such as BCG, interleukin-2 (IL-2), and interferon-alfa • Immunomodulating drugs, for instance, thalidomide and lenalidomide • Cancer vaccines (active specific immunotherapies). In 2010, the FDA approved the first vaccine to treat cancer (the Provenge® vaccine for advanced prostate cancer); other vaccines for many different types of cancer are being studied. List of Chemotherapy Drugs The following table provides a thorough list of the chemotherapy drugs by name.23 Individual Drugs Combination Regimen Abraxane ABVD Amsacrine AC Azacitidine BEAM Bendamustine BEP Bleomycin Capecitabine & docetaxel Busulfan Carbo MV Cabazitaxel Carboplatin & etoposide Capecitabine CAV Carboplatin ChlVPP Carmustine CHOP Chlorambucil Cisplatin, capecitabine & Cisplatin Cladribine Cisplatin & fluorouracil Clofarabine Cisplatin & topotecan Crisantaspase CMF Cyclophosphamide CTD Cytarabine CVP trastuzumab nursece4less.com nursece4less.com nursece4less.com nursece4less.com 33 Dacarbazine de Gramont Dactinomycin DHAP Daunorubicin Docetaxel & carboplatin Docetaxel Docetaxel & cisplatin Doxorubicin Doxorubicin & ifosfamide Epirubicin E-CMF Etoposide EC Fludarabine ECF Fluorouracil ECX Gemcitabine EOX Gliadel implants ESHAP Hydroxycarbamide Etoposide & cisplatin Idarubicin FCR Ifosfamide FEC Irinotecan FEC-T Leucovorin FOLFIRINOX Liposomal daunorubicin GemCap Liposomal doxorubicin GemCarbo Lomustine Gemcitabine & cisplatin Melphalan GemTaxol Mercaptopurine Hyper-CVAD Mesna ICE Methotrexate Irinotecan & cetuximab Mitomycin Irinotecan with 5FU & folinic acid Mitotane MIC Mitoxantrone MM Oxaliplatin MMM Paclitaxel MPT Pemetrexed MVAC Pentostatin MVP Procarbazine Oxaliplatin with 5FU & folonic acid Raltitrexed Oxaliplatin & capecitabine (XELOX Rasburicase Streptozocin Paclitaxel & carboplatin Tegafur-uracil Pemetrexed & cisplatin or CAPOX) nursece4less.com nursece4less.com nursece4less.com nursece4less.com 34 Temozolomide PCV Thiotepa PMitCEBO Tioguanine POMB/ACE Topotecan R-CHOP Trabectedin R-CVP Treosulfan R-DHAP Vinblastine R-ESHAP Vincristine R-ICE Vindesine TAC Vinorelbine TC TIP VAD Vinorelbine & carboplatin Vinorelbine & cisplatin Drug Side Effects Although the specific side effects may differ depending on the type of chemotherapy used, many patients will experience a range of common symptoms. Chemotherapy damages normal cells, which causes the range of side effects experienced, such as nausea, vomiting, lethargy, headaches, and hair loss. The normal cells most likely to be damaged are those that divide rapidly, for instance:29 Bone marrow/blood cells Cells of hair follicles Cells lining the digestive tract Cells lining the reproductive tract nursece4less.com nursece4less.com nursece4less.com nursece4less.com 35 New and Emerging Treatment Strategies There is ongoing research in the area of brain and spinal cord tumors. Medical scientists are looking for causes and ways to prevent them, and physicians are working to improve treatments. Understanding Gene Changes in Tumors Researchers continue to look for the gene changes inside cells that result in brain and spinal cord tumors. The hope is that learning more about these gene changes may lead to better ways to treat these tumors. For example, researchers have found that medulloblastomas can be divided into 4 main types, based on the different gene changes in the tumor cells. Some of these tumor types have a better outlook than others. Physicians are now learning how to use this information to help decide which individual might need more or less intensive treatment.30,31 More recently, researchers have identified some of the specific gene changes found in each type of medulloblastoma that might help the tumor cells grow. Some of these gene changes can be targeted with new types of drugs, which are now being tested in clinical trials. In the future, physicians may be able to develop other drugs that specifically target these gene changes.32 Imaging and Surgical Treatment Recent advances in imaging and surgery techniques for brain tumors have made these procedures much safer and more successful. Often imaging and surgery may be combined with other medical treatment of brain tumors. Some of these techniques are highlighted here. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 36 Functional Magnetic Resonance Imaging Functional Magnetic Resonance Imaging can identify the site of important areas of the brain and how close they are to the tumor. Magnetic Resonance Spectroscopic (MRS) Imaging Specially processed MRS imaging information is used to make a map of important chemicals involved in tumor metabolism. This is being developed to help surgeons direct their biopsies to the most abnormal areas in the tumor and to help doctors direct radiation and evaluate the effects of chemotherapy or targeted therapy. Fluorescence-guided Surgery In fluorescence-guided surgery, the patient drinks a special dye a few hours before surgery. The dye is taken up mainly by the tumor, which then glows when the surgeon looks at it under special lighting from the operating microscope. This lets the surgeon better separate tumor from normal brain tissue. Newer Surgical Approaches For some types of tumors, a new surgical approach is needed. For example, in the treatment of some tumors in or near the pituitary (such as some craniopharyngiomas), an endoscope is used, which is a thin tube with a tiny video camera lens at the tip. The endoscope is passed through a hole made in the back of the nose, which allows the surgeon to operate through the nasal passages and limits the potential damage to the brain. A similar technique can be used for some tumors in the ventricles, where a small opening in the skull near the hairline serves as the point of endoscope insertion. The use of this technique is nursece4less.com nursece4less.com nursece4less.com nursece4less.com 37 limited by the tumor’s size, shape, position, and by how many blood vessels it contains.33,34 Radiation Therapy Several newer types of radiation therapy now let physicians aim radiation more precisely at the tumor, which helps spare normal brain tissue from getting too much radiation. The brain is very sensitive to radiation, which can lead to side effects if normal brain tissue receives a large dose, especially if the child is very young. Clinical trials have shown that in some situations, using chemotherapy can let doctors use lower doses of radiation therapy without lowering the chance that treatment will be effective. Physicians are now trying to determine if even lower doses of radiation can be used and still give the same results.35 Chemotherapy New approaches may help make chemotherapy (chemo) more useful against brain and spinal cord tumors.27,28 Adjuvant Chemotherapy In some individuals with brain tumors, chemo is given right after surgery to either delay radiation therapy (particularly in infants) or to decrease the radiation dose needed to treat the tumor. This is known as adjuvant chemotherapy. Some studies are looking at whether giving prolonged chemo can help avoid the need for radiation therapy at all in certain cases. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 38 High-dose Chemotherapy and Stem Cell Transplant One of the main factors that limit the doses of chemo that can be given safely is its effect on the bone marrow where new blood cells are normally made. A stem cell transplant is a procedure whereby healthy bone marrow stem cells are transplanted to replace damaged or destroyed bone marrow. This allows higher doses of chemo to be given than would normally be possible. First, blood stem cells are removed from either the individual’s blood or the bone marrow and are stored in a deep freeze. The patient is then treated with very high doses of chemo. The blood stem cells are then thawed and infused back into the body, where they settle in the bone marrow and start making new blood cells. Although some individuals with certain brain or spinal cord tumors (such as medulloblastomas) have responded well to this very intensive treatment, it can have serious side effects, and it is not yet known if it is effective enough to become standard. For now, most physicians consider this treatment experimental for brain and spinal tumors. Clinical trials are being done to determine how useful it is. Improving Chemotherapy Drugs Many chemo drugs are limited in their effectiveness because the tightly controlled openings in the brain capillaries, sometimes referred to as the blood-brain barrier, prevents them from getting from the bloodstream to some parts of the brain tumor. Researchers are now trying to modify some of these drugs by coating them with tiny layers of fat (liposomes) or attaching them to molecules that normally cross the blood-brain barrier, to help them work better. This is an area of active research. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 39 Chemotherapy Direct Administration to Tumors Some newer approaches might help physicians get chemotherapy (chemo) directly to brain and spinal cord tumors. For example, in one method called convection enhanced delivery, small tubes are placed into the tumor in the brain through a small hole in the skull during surgery. The tubing extends through the scalp and is connected to an infusion pump, through which chemo drugs can be given. This can be done for hours or days and might be repeated more than once, depending on the drug used. This technique can also be used to get other, newer types of drugs into the tumor. This is still an investigational method, and studies are continuing. Imaging and Tumor Monitoring Procedures Physicians may use a variety of techniques in order to determine what a brain tumor looks like both before and during surgery. Specialized images can be generated that shows what functions the brain tissue near the cancer is responsible for. Generating images both before and during surgery can increase the likelihood that extensive tumor removal can be achieved while avoiding these critical areas.33 Before surgery, the location of the brain tumor in relation to other structures and blood vessels must be determined as precisely as possible. To achieve this, a variety of tests are performed. These may include: Computerized tomography (CT) Magnetic resonance imaging (MRI) Positron emission tomography (PET) Angiography (to map blood vessels) nursece4less.com nursece4less.com nursece4less.com nursece4less.com 40 Using the information obtained from these tests, the surgeon can plan and even rehearse the operation in order to obtain optimal results. Evaluation of outcomes in elderly patients who had undergone surgery for brain tumors indicated that those who underwent preoperative MRI experienced better outcomes than those patients who were not evaluated with MRI before surgery.35 The scans taken before surgery yield a great deal of information, but they do not always provide the precision needed to avoid critical areas of the brain during the operation. Sophisticated mapping techniques can improve the safety and effectiveness of surgery by locating the exact areas of the brain responsible for speech, comprehension, sensation, or movement. Brain mapping is also used to help identify the margin of the tumor and to differentiate between tumor, swelling (edema), and normal tissue. Techniques for brain mapping include:36,37 Direct cortical stimulation Evoked potentials Functional MRI Intraoperative ultrasound imaging Microsurgery These techniques are described more fully below:33,36,38-42 Direct Cortical Stimulation In direct cortical stimulation, a probe passes a tiny electrical current into the brain and delicately stimulates a specific area. The result is a response from the body, such as a visible movement of the corresponding body part. This technique may be employed during nursece4less.com nursece4less.com nursece4less.com nursece4less.com 41 surgery to help identify important functional areas. For example, direct cortical stimulation has been used during surgery for gliomas to successfully identify and preserve cortical areas responsible for language and minimize damage to motor function. Evoked Potentials The electrical response of the brain can be measured by stimulating the brain and measuring the resulting activity, or evoked potentials, on brain scanning equipment. Evoked potentials may be used to map and continuously monitor areas of the brain during surgery. Functional Magnetic Resonance Imaging Magnetic resonance imaging (MRI) is a high-speed imaging device that generates images of the tumor’s use of oxygen. This helps distinguish between active, normal brain, and non-active tumor or dead tissue (necrosis). Functional MRI can be an alternative to direct cortical stimulation. Research indicates that motor and sensory areas identified with functional MRI are very similar to locations identified with direct cortical stimulation. This technique is reliable but requires sophisticated and expensive equipment. Intraoperative Ultrasound Imaging The use of ultrasound during surgery can help determine the depth of the tumor and its diameter. Ultrasound works by sending ultrasonic wave pulses into the brain, which then reflect back to a device. A computer measures the amount of time it takes for the “echoes” to return, and the results are displayed as a TV image. Surgeons can monitor their movements to verify positioning and results during nursece4less.com nursece4less.com nursece4less.com nursece4less.com 42 surgery. The waves can also reflect motion such as blood flow. Ultrasound can make it easier for the surgeon to locate the margins of the tumor so that more extensive tumor removal can be achieved. It helps distinguish between tumor, necrosis (dead tumor cells), cysts, edema, and normal brain. Because ultrasound does not readily penetrate bone, it cannot be used preoperatively. Microsurgery Microsurgery involves the use of a high-powered microscope during surgery, which allows the surgeon to obtain a magnified view of the surgical field. Microsurgery is widely used for brain tumor surgery. Newer Drugs Used In Targeted Therapy As researchers have learned more about the gene changes in tumor cells that help them grow, they have developed newer drugs that target these changes. These targeted drugs work differently from standard chemo drugs. One example of such a targeted drug is everolimus, which may shrink or slow the growth of subependymal giant cell astrocytomas (SEGAs) that can’t be removed with surgery. Some types of medulloblastomas tend to have mutations (changes) in genes that are part of a cell signaling route called the hedgehog pathway. The hedgehog pathway is crucial for the development of the embryo and fetus, but it can be overactive in some medulloblastoma cells. Drugs that target proteins in this pathway are now being tested against medulloblastoma in clinical trials. Many other targeted drugs are already being used to treat other types of cancer, and some are being studied to see if they will work for brain tumors as well. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 43 Angiogenesis Inhibitors Tumors have to create new blood vessels (a process called angiogenesis) to keep their cells nourished. New drugs that attack these blood vessels are used to help treat some cancers, including some brain tumors in adults. Several drugs that impair blood vessel growth are now being studied for use against brain tumors in children.43 Hypoxic Cell Sensitizers Some drugs increase the oxygen content in the tumor, which makes tumor cells more likely to be killed by radiation therapy if the drugs are given before treatment. Studies are now looking to see if this affects treatment outcomes.44 Immunotherapy The goal of immunotherapy is to make the body’s own immune system fight the tumor. Several types of vaccines are being developed against brain tumor cells. Unlike vaccines against infectious diseases, these vaccines are meant to help treat the disease instead of prevent it. The goal of the vaccines is to stimulate the body’s immune system to attack the brain tumor cells. Early study results of some of these vaccines have shown promise, but more research is needed to determine how effective they are. At this time, brain tumor vaccines are available only through clinical trials. Other types of drugs that affect the immune system, such as lenalidomide, are also being studied.45,46 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 44 Therapeutic Viruses Researchers have done a great deal of lab work with viruses that reproduce only within brain tumor cells and then cause those cells to die, while leaving normal cells alone. Research using these viruses in humans with brain tumors is still in very early stages.47,48 Tumor Treating Fields Tumor treating fields (TTFields) is an FDA-approved novel therapeutic option, which studies have shown slows and reverses tumor growth by inhibiting mitosis (the process by which cells divide and replicate). The TTFields option was recently approved in the U.S., for glioblastoma (GBM) in combination with temozolomide for the treatment of newly diagnosed adult patients. Usually treatment with TTFields follows surgery and radiation therapy. Tumor treating fields is also approved in the U.S., for treatment of recurrent GBM as a monotherapy after surgical and radiation options have been exhausted.49 Adhesive bandages hold insulated ceramic discs (transducer arrays) that deliver electricity transformed into electromagnetic energy to the scalp. The battery operated-TTF device generates low intensity, intermediate frequency, alternating electrical fields to the brain. These electrical fields exert selective toxicity in proliferating cells thereby halting cell division and destroying the cancer cells.50 Currently, a physician must prescribe the TTField device. The prescribing physician will provide instructions for using the device, replacing transducer arrays (every 4 to 7 days), and recharging and replacing batteries. Patients must wear the device for at least 18 hours a day, taking only short breaks for personal needs, and use the device for at least four weeks.49 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 45 Other New Treatment Strategies Researchers are also testing some newer approaches to treatment that may help physicians target tumors more precisely. The hope is to develop more effective treatments that cause fewer side effects. Although these treatment approaches are promising, most are still experimental at this time and are only available through clinical trials. Summary The field of brain tumor research, diagnosis, and treatment is rapidly evolving. The number and types of brain tumors continues to increase. Brain tumors are diagnosed by conducting a neurologic exam and tests that include MRI, CT scan, and biopsy. Treatment options include watchful waiting, radiation therapy, chemotherapy, and targeted therapy as well as surgery. Targeted therapy has been highlighted here and uses substances that attack cancer cells without harming normal cells. Combination therapy is often done, which may incorporate diagnostic and surgical approaches. As the research on brain tumors grows, so does the ability to improve screening, diagnose and target treatment to provide patients with optimal outcomes. It is essential that health clinicians understand surgery and treatment options in order to communicate it to their patients and to develop a care plan that has a positive outcome while respecting the patient's needs and desires. Please take time to help NurseCe4Less.com course planners evaluate the nursing knowledge needs met by completing the self-assessment of Knowledge Questions after reading the article, and providing feedback in the online course evaluation. Completing the study questions is optional and is NOT a course requirement. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 46 1. Over ________ types of brain tumors have been identified to date, and that number continues to increase. a. b. c. d. 30 four 60 120 2. The choice of antiepileptic drugs is challenging for patients with brain tumor-related epilepsy (BTRE) because BTRE a. b. c. d. is untreatable. is often drug-resistant. requires surgery as the first line of treatment. is caused by the presence of a tumor. 3. In brain tumor patients, the presence of _________ is considered the most important risk factor for long-term disability. a. b. c. d. a cerebral edema depression a comorbidity epilepsy 4. Among the recently marketed drugs, ___________ has demonstrated promising results and should be considered a possible treatment option for BTRE. a. b. c. d. lacosamide carbamazepine phenobarbital phenytoin 5. True or False: In patients with a brain tumor, seizures are the onset symptom in 20-40% of patients, while a further 20-45% of patients will present seizures during the course of the disease. a. True b. False nursece4less.com nursece4less.com nursece4less.com nursece4less.com 47 6. For some patients, antiepileptic drugs may have a secondary, “positive” effect; for example, ___________ may have a sedative effect in patients who are agitated. a. b. c. d. oxcarbazepine carbamazepine pregabalin phenytoin 7. Newer antiepileptic drugs, such as _______________, can be used as first choice therapies in monotherapy because they do not have the side effects of some of the older drugs. a. b. c. d. levetiracetam carbamazepine phenobarbital phenytoin 8. The steroids given to brain tumor patients are a. b. c. d. the same as the steroids to build muscle. corticosteroids. synthetic steroids. All of the above 9. In brain tumor treatment, steroids are used to ____________________________, which is/are sometimes caused by the tumor or its treatment. a. b. c. d. increase energy to combat lethargy control bleeding reduce brain swelling, or cerebral edema reduce epileptic conditions 10. Which of the older antiepileptic drugs can be considered a first choice therapy in a monotherapy context? a. b. c. d. Lamotrigine Valproic acid (VPA) Phenobarbital Phenytoin nursece4less.com nursece4less.com nursece4less.com nursece4less.com 48 11. True or False: Healthcare practitioners need to appreciate the fact that taking care of brain tumorrelated epilepsy patients means finding a cure for the patient. a. True b. False 12. An antiepileptic drug may have a secondary, “positive” effect such as ______________, which will elevate mood in depressed patients. a. b. c. d. oxcarbazepine topiramate pregabalin phenytoin 13. Dexamethasone and prednisone are the most commonly used a. b. c. d. antiepileptic drugs. mood stabilizers. antidepressants. corticosteroid drugs. 14. Steroids are used for short-term symptom control although they may occasionally be continued for a. b. c. d. a period of weeks. months. Answers a., and b., above None of the above 15. Because corticosteroids are hormones (that are produced _____________________), their long-term use requires close monitoring. a. b. c. d. by the pituitary gland synthetically by the adrenal glands by the hypothalamus nursece4less.com nursece4less.com nursece4less.com nursece4less.com 49 16. Steroids may be prescribed for brain tumor patients a. b. c. d. when a brain mass is discovered. around the time of surgery with radiation or chemotherapy. All of the above 17. True or False: Corticosteroid can temporarily improve neurological symptoms by reducing brain swelling and in most cases treat or reduce the tumor. a. True b. False 18. The dose of corticosteroid used in brain tumor patients is dependent on ________________ seen on the MRI or CT scan of the brain. a. b. c. d. the size of the tumor the location of the tumor the type of tumor how much swelling is 19. When the patient no longer requires steroid treatment, steroids a. b. c. d. may be stopped abruptly. must be gradually reduced. must be replaced by synthetic steroids. produced by the adrenal glands immediately take over. 20. Steroids can cause a wide range of unwanted effects. The most common side effect(s) caused by steroid treatment is/are a. b. c. d. increased appetite. weight loss. decreased blood sugar levels. All of the above nursece4less.com nursece4less.com nursece4less.com nursece4less.com 50 21. Steroid treatment can interact with other medications, which may a. b. c. d. increase the steroid levels in the patient’s blood. decrease the steroid levels in the patient’s blood. increase the side effects of the steroids. All of the above 22. Steroids may be prescribed to eliminate cancer cells in patients diagnosed with a. b. c. d. medulloblastomas. hydrocephaly. primary central nervous system lymphoma (PCNSL). cerebral edema. 23. True or False: Steroids can also be used in brain tumor patients for other reasons: to improve appetite, prevent nausea and vomiting from chemotherapy, reduce pain and prevent allergic reactions to some chemotherapies. a. True b. False 24. Radiation treatment disrupts the cancer cells: it prevents them from dividing and growing, by creating small breaks in the cell’s DNA by a. b. c. d. creating hypoxia that starves cancer cells of oxygen. cutting the blood supply to the cancer cells. delivering high-energy particles or waves to the cells. injecting a chemical composition into the cancer cells. 25. Radiation treatment is especially favorable for cancer that a. b. c. d. has metastasized. is diffused because radiation has a broad exposure. is located in one region of the body. is close to or intertwined with healthy tissue. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 51 26. Which of the following may be an acute side effect associated with radiation cancer treatment? a. b. c. d. Fibrosis Damage to the salivary glands Memory loss Infertility 27. ___________________ is a rare, chronic side effect of radiation treatment. a. b. c. d. Fatigue Hair loss Infertility A second cancer 28. Girls treated with radiation to the chest for Hodgkin lymphoma have an increased risk of developing _____________ later in life. a. b. c. d. medulloblastomas primary central nervous system lymphoma liver cancer breast cancer 29. True or False: Patients should take steroid treatment on an empty stomach in order receive the maximum benefit from the treatment. a. True b. False 30. External-beam radiation therapy is most often delivered in the form of photon beams, which is a. b. c. d. made up of protons. either x-rays or gamma rays. also known as brachytherapy. also called inverse treatment therapy. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 52 31. With intensity-modulated radiation therapy (IMRT) the radiation oncologist chooses a. b. c. d. the number of radiation beams. the angles of the radiation beams. the radiation doses. All of the above 32. ___________________ is a type of image-guided intensity-modulated radiation therapy (IMRT). a. b. c. d. Tomotherapy Brachytherapy Forward treatment Internal radiation therapy 33. A tomotherapy machine is a hybrid between _______________ and an external-beam radiation therapy machine. a. b. c. d. an X-ray a particle accelerator a traditional forward treatment plan a CT imaging scanner 34. True or False: In general, the lifetime risk of a second cancer is highest in people treated for cancer with radiation therapy as children or adolescents. a. True b. False 35. Which of the following procedures is most likely to damage normal tissue from high radiation doses? a. b. c. d. Tomotherapy Image-guided radiation therapy Intensity-modulated radiation therapy Three-dimensional conformal radiotherapy nursece4less.com nursece4less.com nursece4less.com nursece4less.com 53 36. With Image-guided radiation therapy (IGRT), repeated imaging scans are performed during treatment, which are processed by computers to identify a. b. c. d. post-treatment, normal tissue damage. the type of tumor. changes in a tumor’s size and location. whether the tumor is benign or malignant. 37. ___________________ can be used to treat only small tumors with well-defined edges. a. b. c. d. Tomotherapy Brachytherapy Stereotactic radiosurgery (SRS) Internal radiation therapy 38. Photons and protons differ in a. b. c. d. only protons use x-rays or gamma rays. the way they deposit energy in living tissue. that photons are used intracavitarily. All of the above 39. True or False: During traditional (forward) treatment planning, the radiation oncologist chooses the number and angles of the radiation beams in advance and computers calculate how much dose will be delivered from each of the planned beams. a. True b. False 40. Stereotactic body radiation therapy (SBRT) treats tumors that lie a. b. c. d. within the brain stem. within the cerebrum. outside the brain and spinal cord. outside the pituitary gland. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 54 41. _________________ is a radiation treatment that uses radioactive materials placed inside or on the body. a. b. c. d. Image-guided radiation therapy (IGRT) External-beam radiation therapy Stereotactic radiosurgery (SRS) Brachytherapy 42. In brachytherapy, radioactive isotopes, sealed in tiny pellets or “seeds,” are placed in patients and they give off radiation that damages nearby cancer cells because a. b. c. d. isotopes have differing numbers of protons. isotopes have the same number of neutrons. the isotopes deposit energy. the isotopes decay naturally. 43. Adjuvant chemotherapy is used in some individuals with brain tumors, after surgery, a. b. c. d. to delay or decrease radiation therapy. in lieu of radiation treatment. because chemo does not damage healthy cells. because radiation is not easily delivered to infants. 44. True or False: Episcleral brachytherapy uses a radiation source that is attached to the liver. a. True b. False 45. Chemotherapy drugs are similar in the following way: a. b. c. d. they they they they are similar in their chemical composition. are taken in the same way, i.e., intravenously. damage the cancer cells to prevent reproduction. have similar side effects. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 55 46. Adjuvant chemotherapy refers to chemotherapy that is used _________________ to reduce the risk of cancer coming back by treating any remaining cells. a. b. c. d. after surgery or radiotherapy with radiotherapy in lieu of radiotherapy before surgery or radiotherapy 47. _______________ are a class of chemotherapy drugs that interfere with DNA and RNA growth by substituting for the normal building blocks of RNA and DNA. a. b. c. d. Antimetabolites Alkylating agents Anthracyclines Anti-tumor antibiotics 48. A major consideration when giving or using ________________ is that they can permanently damage the heart if given in high doses. a. b. c. d. alkylating agents topoisomerase inhibitors anthracyclines immunotherapies 49. True or False: Chemotherapy drugs used to treat cancer damage cancer cells and non-cancer cells alike. a. True b. False 50. Passive immunotherapies a. b. c. d. the body’s immune system to attack the disease. use immune system components created outside the body. stimulate the body’s immune system. are integrally part of chemotherapy. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 56 51. With the use of stem cell transplants, higher doses of chemo may be given than would normally be possible because stem cells a. b. c. d. substitute the DNA and RNA building blocks. neutralize chemotherapy drugs. replace damaged or destroyed bone marrow. are not affected by the blood-brain barrier. 52. Many chemo drugs are limited in their effectiveness because the ________________ prevent(s) them from getting from the bloodstream to some parts of the brain tumor. a. b. c. d. blood-brain barrier white blood cells the patient’s immune system fat cells 53. The MRI is a high-speed imaging device that generates images of the tumor’s use of a. b. c. d. metabolites. fat cells. oxygen. therapeutic viruses. 54. The use of ultrasound during surgery can help determine the a. b. c. d. depth of the tumor and its diameter. tumor’s use of oxygen. tumor’s response to radiation therapy. tumor’s ability to replicate cells. 55. True or False: Individuals with certain brain or spinal cord tumors (such as medulloblastomas) have responded well to high doses of chemo followed by stem cell transplant so this treatment has become standard. a. True b. False nursece4less.com nursece4less.com nursece4less.com nursece4less.com 57 CORRECT ANSWERS: 1. Over ________ types of brain tumors have been identified to date, and that number continues to increase. d. 120 p. 5: “Over 120 types of brain tumors have been identified to date, and that number continues to increase.” 2. The choice of antiepileptic drugs is challenging for patients with brain tumor-related epilepsy (BTRE) because BTRE b. is often drug-resistant. p. 6: “The choice of antiepileptic drugs is challenging for this particular patient population because brain tumor-related epilepsy (BTRE) is often drug-resistant.” 3. In brain tumor patients, the presence of _________ is considered the most important risk factor for long-term disability. d. epilepsy p. 6: “In brain tumor patients, the presence of epilepsy is considered the most important risk factor for long-term disability.” 4. Among the recently marketed drugs, ___________ has demonstrated promising results and should be considered a possible treatment option for BTRE. a. lacosamide p. 6: “Among the recently marketed drugs, lacosamide has demonstrated promising results and should be considered a possible treatment option.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com 58 5. True or False: In patients with a brain tumor, seizures are the onset symptom in 20-40% of patients, while a further 20-45% of patients will present seizures during the course of the disease. a. True p. 6: “In patients with a brain tumor (BT), seizures are the onset symptom in 20-40% of patients, while a further 2045% of patients will present them during the course of the disease.” 6. For some patients, antiepileptic drugs may have a secondary, “positive” effect; for example, ___________ may have a sedative effect in patients who are agitated. c. pregabalin p. 7: “For some patients, antiepileptic drugs may have a secondary, “positive” effect; for example, pregabalin or topiramate may have a sedative effect in patients who are agitated, while oxcarbazepine or lamotrigine will elevate mood in depressed patients.” 7. Newer antiepileptic drugs, such as _______________, can be used as first choice therapies in monotherapy because they do not have the side effects of some of the older drugs. a. levetiracetam p. 7: “The newer antiepileptic drugs, such as lamotrigine, levetiracetam, oxcarbazepine, topiramate and the older antiepileptic drugs, valproic acid (VPA), can be considered first choice therapies in monotherapy, for all of the reasons previously discussed.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com 59 8. The steroids given to brain tumor patients are b. corticosteroids. p. 8: “The steroids given to brain tumor patients are corticosteroids – hormones produced by the adrenal glands. They are not the same as the anabolic steroids used by athletes to build muscle.” 9. In brain tumor treatment, steroids are used to ____________________________, which is/are sometimes caused by the tumor or its treatment. c. reduce brain swelling, or cerebral edema p. 8: “Steroids are naturally occurring substances. In brain tumor treatment, steroids are used to reduce the brain swelling, or cerebral edema, sometimes caused by the tumor or its treatment.” 10. Which of the older antiepileptic drugs can be considered a first choice therapy in a monotherapy context? b. Valproic acid (VPA) p. 7: “The newer antiepileptic drugs, such as lamotrigine, levetiracetam, oxcarbazepine, topiramate and the older antiepileptic drugs, valproic acid (VPA), can be considered first choice therapies in monotherapy, for all of the reasons previously discussed.” 11. True or False: Healthcare practitioners need to appreciate the fact that taking care of brain tumorrelated epilepsy patients means finding a cure for the patient. b. False p. 8: “Healthcare practitioners need to appreciate the fact that ‘taking care of’ these patients does not mean ‘curing’ as much as it means recognizing and responding to the needs of each unique individual.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com 60 12. An antiepileptic drug may have a secondary, “positive” effect such as ______________, which will elevate mood in depressed patients. a. oxcarbazepine pp. 7-8: “For some patients, antiepileptic drugs may have a secondary, “positive” effect; for example, pregabalin or topiramate may have a sedative effect in patients who are agitated, while oxcarbazepine or lamotrigine will elevate mood in depressed patients.” 13. Dexamethasone and prednisone are the most commonly used d. corticosteroid drugs. p. 8: “Dexamethasone and prednisone are the most commonly used corticosteroid drugs.” 14. Steroids are used for short-term symptom control although they may occasionally be continued for a. b. c. d. a period of weeks. months. Answers a., and b., above None of the above p. 9: “Steroids are used for short-term symptom control although they may occasionally be continued for a period of weeks or months.” 15. Because corticosteroids are hormones (that are produced _____________________), their long-term use requires close monitoring. c. by the adrenal glands p. 8: “The steroids given to brain tumor patients are corticosteroids – hormones produced by the adrenal glands…. Because steroids are hormones, their long-term use requires close monitoring.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com 61 16. Steroids may be prescribed for brain tumor patients a. b. c. d. when a brain mass is discovered. around the time of surgery with radiation or chemotherapy. All of the above p. 8: “Steroids may be prescribed when a brain mass is seen on an MRI or CT scan of the brain, around the time of surgery or radiation, or sometimes with chemotherapy.” 17. True or False: Corticosteroid can temporarily improve neurological symptoms by reducing brain swelling and in most cases treat or reduce the tumor. b. False p. 8: “These steroids can temporarily improve neurological symptoms by reducing brain swelling but in most cases do not directly treat the tumor.” p. 9: “Steroids are usually administered intravenously (IV) or by mouth (orally)…. The dose used is dependent on how much swelling is seen on the MRI or CT scan of the brain. 18. The dose of corticosteroid used in brain tumor patients is dependent on ________________ seen on the MRI or CT scan of the brain. d. how much swelling is p. 9: “Steroids are usually administered intravenously (IV) or by mouth (orally).… The dose used is dependent on how much swelling is seen on the MRI or CT scan of the brain.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com 62 19. When the patient no longer requires steroid treatment, steroids b. must be gradually reduced. pp. 9-10: “When the patient no longer requires steroids, he or she will be given instructions to slowly taper and stop the drug. Patients should not abruptly stop taking their steroids. A gradual reduction of steroid dose allows the body to begin producing its own steroids again. This gradual tapering avoids adrenal crisis, which is caused by insufficient levels of the hormone cortisol.” 20. Steroids can cause a wide range of unwanted effects. The most common side effect(s) caused by steroid treatment is/are a. increased appetite. p. 10: “Steroids can cause a wide range of unwanted effects. The most common side effects include increased appetite, weight gain, increased blood sugar levels (especially in patients who have diabetes), gastrointestinal problems (like stomach ulcers), frequent urination, insomnia and mood changes like irritability or mania, muscle weakness, susceptibility to infections like pneumonia, thinning of the skin, and acne.” 21. Steroid treatment can interact with other medications, which may a. b. c. d. increase the steroid levels in the patient’s blood. decrease the steroid levels in the patient’s blood. increase the side effects of the steroids. All of the above p. 10: “Steroids can interact with other medications, either increasing or decreasing the levels in the patient’s blood, which can alter their effectiveness or increase their side effects.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com 63 22. Steroids may be prescribed to eliminate cancer cells in patients diagnosed with c. primary central nervous system lymphoma (PCNSL). p. 9: “In the case of most brain tumors, steroids are not prescribed to eliminate cancer cells. One exception is primary central nervous system lymphoma (PCNSL), which is a lymphoma involving the brain or spinal cord.” 23. True or False: Steroids can also be used in brain tumor patients for other reasons: to improve appetite, prevent nausea and vomiting from chemotherapy, reduce pain and prevent allergic reactions to some chemotherapies. a. True pp. 8-9: “Steroids can also be used for other reasons. They can improve appetite, prevent nausea and vomiting from chemotherapy, reduce pain and prevent allergic reactions to some chemotherapies.” 24. Radiation treatment disrupts the cancer cells: it prevents them from dividing and growing, by creating small breaks in the cell’s DNA by c. delivering high-energy particles or waves to the cells. p. 10: “Radiation is a common treatment method for individuals who are able to tolerate it. This treatment is delivered using high-energy particles or waves that disrupt the cancer. These particles create small breaks in the DNA that is inside the cells, which prevent the cancer cells from dividing and growing.” 25. Radiation treatment is especially favorable for cancer that c. is located in one region of the body. p. 11: “Radiation is especially favorable for cancer that is located in one region of the body as it can be delivered as a localized treatment.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com 64 26. Which of the following may be an acute side effect associated with radiation cancer treatment? b. Damage to the salivary glands p. 16: “The following is a description of the most common acute and chronic side effects associated with radiation: Acute - Acute radiation side effects are caused by damage to rapidly dividing normal cells in the area being treated. These effects include skin irritation or damage at regions exposed to the radiation beams. Examples include damage to the salivary glands or hair loss when the head or neck area is treated, or urinary problems when the lower abdomen is treated. Most acute effects disappear after treatment ends, though some (like salivary gland damage) can be permanent.” 27. ___________________ is a rare, chronic side effect of radiation treatment. d. A second cancer p. 17: “Chronic - Late side effects of radiation therapy may or may not occur. Depending on the area of the body treated, late side effects can include: … Rarely, a second cancer caused by radiation exposure.” 28. Girls treated with radiation to the chest for Hodgkin lymphoma have an increased risk of developing _____________ later in life. d. breast cancer p. 17: “For example, girls treated with radiation to the chest for Hodgkin lymphoma have an increased risk of developing breast cancer later in life.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com 65 29. True or False: Patients should take steroid treatment on an empty stomach in order receive the maximum benefit from the treatment. b. False p. 9: “To protect the stomach, patients should take their steroids with food or milk. An additional medication may also be prescribed to further protect the stomach.” 30. External-beam radiation therapy is most often delivered in the form of photon beams, which is b. either x-rays or gamma rays. p. 12 “External-beam radiation therapy is most often delivered in the form of photon beams (either X-rays or gamma rays).” 31. With intensity-modulated radiation therapy (IMRT) the radiation oncologist chooses c. the radiation doses. p. 12: “Unlike other types of radiation therapy, IMRT is planned in reverse (called inverse treatment planning). In inverse treatment planning, the radiation oncologist chooses the radiation doses to different areas of the tumor and surrounding tissue, and then a high-powered computer program calculates the required number of beams and angles of the radiation treatment.” 32. ___________________ is a type of image-guided intensity-modulated radiation therapy (IMRT). a. Tomotherapy p. 13: “Tomotherapy is a type of image-guided IMRT.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com 66 33. A tomotherapy machine is a hybrid between _______________ and an external-beam radiation therapy machine. d. a CT imaging scanner p. 13: “Tomotherapy is a type of image-guided IMRT. A tomotherapy machine is a hybrid between a CT imaging scanner and an external-beam radiation therapy machine.” 34. True or False: In general, the lifetime risk of a second cancer is highest in people treated for cancer with radiation therapy as children or adolescents. a. True p. 17: “Second cancers that develop after radiation therapy depend on the part of the body that was treated. For example, girls treated with radiation to the chest for Hodgkin lymphoma have an increased risk of developing breast cancer later in life. In general, the lifetime risk of a second cancer is highest in people treated for cancer as children or adolescents.” 35. Which of the following procedures is most likely to damage normal tissue from high radiation doses? d. Three-dimensional conformal radiotherapy p. 12: “Compared with three-dimensional conformal radiotherapy (3D-CRT), IMRT can reduce the risk of some side effects, such as damage to the salivary glands (which can cause dry mouth, or xerostomia), when the head and neck are treated with radiation therapy.” p. 13: “Like standard IMRT, tomotherapy may be better than 3D-CRT at sparing normal tissue from high radiation doses.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com 67 36. With Image-guided radiation therapy (IGRT), repeated imaging scans are performed during treatment, which are processed by computers to identify c. changes in a tumor’s size and location. p. 12: “In IGRT, repeated imaging scans (CT, MRI, or PET) are performed during treatment. Imaging scans are processed by computers, identifying changes in a tumor’s size and location due to treatment and allowing patient positioning or planned radiation dose adjusting during treatment.” 37. ___________________ can be used to treat only small tumors with well-defined edges. c. Stereotactic radiosurgery (SRS) p. 13: “Stereotactic radiosurgery (SRS) … can be used to treat only small tumors with well-defined edges.” 38. Photons and protons differ in b. the way they deposit energy in living tissue. p. 13: “Proton beams differ from photon beams mainly in the way they deposit energy in living tissue.” 39. True or False: During traditional (forward) treatment planning, the radiation oncologist chooses the number and angles of the radiation beams in advance and computers calculate how much dose will be delivered from each of the planned beams. a. True p. 12: “In inverse treatment planning, the radiation oncologist chooses the radiation doses to different areas of the tumor and surrounding tissue, and then a high-powered computer program calculates the required number of beams and angles of the radiation treatment. In contrast, during traditional (forward) treatment planning, the radiation oncologist chooses the number and angles of the radiation beams in advance and computers calculate how much dose will be delivered from each of the planned beams.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com 68 40. Stereotactic body radiation therapy (SBRT) treats tumors that lie c. outside the brain and spinal cord. p. 13: “Stereotactic body radiation therapy (SBRT) delivers radiation therapy in fewer sessions, using smaller radiation fields and higher doses than 3D-CRT in most cases. By definition, SBRT treats tumors that lie outside the brain and spinal cord.” 41. _________________ is a radiation treatment that uses radioactive materials placed inside or on the body. d. Brachytherapy P. 14: “Internal radiation therapy (brachytherapy) is radiation delivered from radiation sources (radioactive materials) placed inside or on the body.” 42. In brachytherapy, radioactive isotopes, sealed in tiny pellets or “seeds,” are placed in patients and they give off radiation that damages nearby cancer cells because d. the isotopes decay naturally. p. 14: “In brachytherapy, radioactive isotopes are sealed in tiny pellets or ‘seeds.’ These seeds are placed in patients using delivery devices, such as needles, catheters, or some other type of carrier. As the isotopes decay naturally, they give off radiation that damages nearby cancer cells.” 43. Adjuvant chemotherapy is used in some individuals with brain tumors, after surgery, a. to delay or decrease radiation therapy. p. 38: “Adjuvant chemotherapy … In some individuals with brain tumors, chemo is given right after surgery to either delay radiation therapy (particularly in infants) or to decrease the radiation dose needed to treat the tumor. This is known as adjuvant chemotherapy.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com 69 44. True or False: Episcleral brachytherapy uses a radiation source that is attached to the liver. b. False p. 14: “Episcleral brachytherapy, which is used to treat melanoma inside the eye, uses a source that is attached to the eye.” 45. Chemotherapy drugs are similar in the following way: c. they damage the cancer cells to prevent reproduction. p. 17: “Chemotherapy drugs vary widely in their chemical composition, how they are taken, their usefulness in treating specific forms of cancer, and their side effects. Although these drugs differ in the ways indicated above, they all work to disrupt the ways in which cancer cells divide and grow. The drugs damage the cells to prevent reproduction.“ 46. Adjuvant chemotherapy refers to chemotherapy that is used _________________ to reduce the risk of cancer coming back by treating any remaining cells. a. after surgery or radiotherapy p. 18: “Chemotherapy…. After surgery or radiotherapy to reduce the risk of cancer coming back by treating any remaining cells (called adjuvant chemotherapy).” 47. _______________ are a class of chemotherapy drugs that interfere with DNA and RNA growth by substituting for the normal building blocks of RNA and DNA. a. Antimetabolites p. 27: “Antimetabolites are a class of drugs that interfere with DNA and RNA growth by substituting for the normal building blocks of RNA and DNA.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com 70 48. A major consideration when giving or using ________________ is that they can permanently damage the heart if given in high doses. c. anthracyclines p. 28: “Anthracyclines are anti-tumor antibiotics that interfere with enzymes involved in DNA replication. These drugs work in all phases of the cell cycle. They are widely used for a variety of cancers. A major consideration when giving these drugs is that they can permanently damage the heart if given in high doses.” 49. True or False: Chemotherapy drugs used to treat cancer damage cancer cells and non-cancer cells alike. a. True pp. 17-18: “The drugs damage the cells to prevent reproduction. Unfortunately, chemotherapy drugs also have the same effect on non-cancer cells.” 50. Passive immunotherapies b. use immune system components created outside the body. p. 32: “Passive immunotherapies do not rely on the body to attack the disease; instead, they use immune system components (such as antibodies) created outside the body.” 51. With the use of stem cell transplants, higher doses of chemo may be given than would normally be possible because stem cells c. replace damaged or destroyed bone marrow. p. 39: “A stem cell transplant is a procedure whereby healthy bone marrow stem cells are transplanted to replace damaged or destroyed bone marrow.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com 71 52. Many chemo drugs are limited in their effectiveness because the ________________ prevent(s) them from getting from the bloodstream to some parts of the brain tumor. a. blood-brain barrier p. 39: “Many chemo drugs are limited in their effectiveness because the tightly controlled openings in the brain capillaries, sometimes referred to as the blood-brain barrier, prevents them from getting from the bloodstream to some parts of the brain tumor.” 53. The MRI is a high-speed imaging device that generates images of the tumor’s use of c. oxygen. p. 42: “Magnetic resonance imaging is a high-speed imaging device that generates images of the tumor’s use of oxygen.” 54. The use of ultrasound during surgery can help determine the a. depth of the tumor and its diameter. p. 42: “Intraoperative ultrasound imaging: The use of ultrasound during surgery can help determine the depth of the tumor and its diameter.” 55. True or False: Individuals with certain brain or spinal cord tumors (such as medulloblastomas) have responded well to high doses of chemo followed by stem cell transplant so this treatment has become standard. b. False p. 39: “Although some individuals with certain brain or spinal cord tumors (such as medulloblastomas) have responded well to this very intensive treatment, it can have serious side effects, and it is not yet known if it is effective enough to become standard.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com 72 References The References below include published works and in-text citations of published works that are intended as helpful material for your further reading. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. Aneja S, Sharma S. Newer anti-epileptic drugs. Vol. 50, Indian Pediatrics. 2013. p. 1033–40. Weston J, Greenhalgh J, Marson AG. Antiepileptic drugs as prophylaxis for post-craniotomy seizures. Vol. 3, The Cochrane database of systematic reviews. 2015. p. CD007286. Johnston CA, Crawford PM. Anti-epileptic drugs and hormonal treatments. Curr Treat Options Neurol. 2014;16. Sørensen AT, Kokaia M. Novel approaches to epilepsy treatment. Vol. 54, Epilepsia. 2013. p. 1–10. Belcastro V, Striano P. Antiepileptic drugs, hyperhomocysteinemia and B-vitamins supplementation in patients with epilepsy. Vol. 102, Epilepsy Research. 2012. p. 1–7. Wells EM, Gaillard WD, Packer RJ. Pediatric Brain Tumors and Epilepsy. Vol. 19, Seminars in Pediatric Neurology. 2012. p. 3–8. Nossek E, Matot I, Shahar T, Barzilai O, Rapoport Y, Gonen T, et al. Failed awake craniotomy: a retrospective analysis in 424 patients undergoing craniotomy for brain tumor. J Neurosurg. 2012;118(February):1–7. Eadie MJ. Shortcomings in the current treatment of epilepsy. Expert Rev Neurother. 2012;12:1419–27. Hart MG, Whittle IR, Grant R. Steroids and brain tumors. Handb Clin Neurol. 2012;104:371–9. Witt KA, Sandoval KE. Steroids and the blood-brain barrier: Therapeutic implications. Adv Pharmacol. 2014;71:361–90. Bebawy JF. Perioperative Steroids for Peritumoral Intracranial Edema. J Neurosurg Anesthesiol. 2012;24(3):173–7. Seyfried TN, Flores R, Poff AM, D’Agostino DP, Mukherjee P. Metabolic therapy: A new paradigm for managing malignant brain cancer. Vol. 356, Cancer Letters. 2015. p. 289–300. Phillips EH, Fox CP, Cwynarski K. Primary CNS lymphoma. Curr Hematol Malig Rep. 2014;9(3):243–53. Roth P, Regli L, Tonder M, Weller M. Tumor-associated edema in brain cancer patients: pathogenesis and management. Expert Rev Anticancer Ther. 2013;13(11):1319–25. Kaliberov SA, Buchsbaum DJ. Chapter seven--Cancer treatment with gene therapy and radiation therapy. Adv Cancer Res. 2012;115:221–63. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 73 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. Bernier J, Hall EJ, Giaccia A. Radiation oncology: a century of achievements. Nat Rev Cancer. 2014 Anderson C, Fleming P, Wilkinson A, Singh AD. Principles of Radiation Therapy. In: Clinical Ophthalmic Oncology. 2012. p. 40–4. Zaider M, Hanin L. Tumor control probability in radiation treatment. Med Phys. 2011;38:574–83. Radiation Therapy for Cancer - National Cancer Institute [Internet]. [cited 2014 Dec 15]. Available from: http://www.cancer.gov/cancertopics/factsheet/Therapy/radiation Multhoff G, Radons J. Radiation, Inflammation, and Immune Responses in Cancer. Vol. 2, Frontiers in Oncology. 2012. DeVita VT, Chu E. A history of cancer chemotherapy. Vol. 68, Cancer Research. 2008. p. 8643–53. Cancer Research UK. How Chemotherapy Works. Cancer Research UK. 2013. p. 3. Society AC. What is chemotherapy ? How chemotherapy works. Am Cancer Soc. 2013;1–29. Dy GK, Adjei AA. Principles of chemotherapy. In: Oncology: An Evidence-Based Approach. 2013. p. 14–40. Chabner BA, Roberts TG. Chemotherapy and the war on cancer. Nat Rev Cancer. 2015;5:65–72. Caley A, Jones R. The principles of cancer treatment by chemotherapy. Vol. 30, Surgery. 2012. p. 186–90. Greenhalgh TA, Symonds RP. Principles of chemotherapy and radiotherapy. Vol. 24, Obstetrics, Gynaecology and Reproductive Medicine. 2014. p. 259–65. Snozek CLH. Pharmacogenetics and Cancer Chemotherapy. In: Pharmacogenomics in Clinical Therapeutics. 2012. p. 39–52. Lung cancer guide book. Chemotherapy side effects profile [Internet]. Lung cancer guide book. 2013. p. 384–95. Available from: http://www.lungcancerguidebook.org/lcguidebook_aug05/append ix_cxtx_side_effects.pdf Millard NE, De Braganca KC. Medulloblastoma. J Child Neurol. 2015;0883073815600866-. Gopalakrishnan V, Tao R-H, Dobson T, Brugmann W, Khatua S. Medulloblastoma development: tumor biology informs treatment decisions. CNS Oncol. 2015;4(2):79–89. Gerber NU, Mynarek M, von Hoff K, Friedrich C, Resch A, Rutkowski S. Recent developments and current concepts in Medulloblastoma. Vol. 40, Cancer Treatment Reviews. 2014. p. 356–65. Mabray MC, Barajas RF, Cha S. Modern brain tumor imaging. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 74 34. 35. 36. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. Brain tumor Res Treat. 2015;3(1):8–23. Bovenberg MSS, Degeling MH, Tannous BA. Advances in stem cell therapy against gliomas. Vol. 19, Trends in Molecular Medicine. 2013. p. 281–91. Juweid ME, Cheson BD. Positron-emission tomography and assessment of cancer therapy. N Engl J Med. 2006;354:496–507. Chung K, Deisseroth K. Why mapping the brain matters. Nat 37. Marx V. Neurobiology: Brain mapping in high resolution. Nature. 2013;503(7474):147–52. Menze BH, Jakab A, Bauer S, Kalpathy-Cramer J, Farahani K, Kirby J, et al. The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS). IEEE Trans Med Imaging. 2015;34(10):1993–2024. Wang J, Liu T. A survey of MRI-based brain tumor segmentation methods. Tsinghua Sci Technol. 2014;19(6):578–95. Bauer S, May C, Dionysiou D, Stamatakos G, Buchler P, Reyes M. Multiscale modeling for image analysis of brain tumor studies. IEEE Trans Biomed Eng. 2012;59(1):25–9. Kennedy J, Schuele SU. Long-term monitoring of brain tumors: When is it necessary’. Epilepsia. 2013;54(SUPPL. 9):50–5. Alivisatos AP, Andrews AM, Boyden ES, Chun M, Church GM, Deisseroth K, et al. Nanotools for neuroscience and brain activity mapping. ACS Nano. 2013;7(3):1850–66. El-Kenawi AE, El-Remessy AB. Angiogenesis inhibitors in cancer therapy: Mechanistic perspective on classification and treatment rationales. Vol. 170, British Journal of Pharmacology. 2013. p. 712–29. Basheer B, Mathew D, George BK, Reghunadhan Nair CP. An overview on the spectrum of sensitizers: The heart of Dye Sensitized Solar Cells. Sol Energy. 2014;108:479–507. Vanneman M, Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Vol. 12, Nature Reviews Cancer. 2012. p. 237–51. Bloch O. Immunotherapy for malignant gliomas. Cancer Treat Res. 2015;163:143–58. Bartlett DL, Liu Z, Sathaiah M, Ravindranathan R, Guo Z, He Y, et al. Oncolytic viruses as therapeutic cancer vaccines. Mol Cancer. 2013;12(1):103. Bauzon M, Hermiston T. Armed therapeutic viruses - A disruptive therapy on the horizon of cancer immunotherapy. Vol. 5, Frontiers in Immunology. 2014. Davis ME. Tumor treating fields - an emerging cancer treatment modality. Clin J Oncol Nurs. 2013;17(4):441–3. Davies AM, Weinberg U, Palti Y. Tumor treating fields: A new nursece4less.com nursece4less.com nursece4less.com nursece4less.com 75 frontier in cancer therapy. Ann N Y Acad Sci. 2013;1291(1):86– 95. The information presented in this course is intended solely for the use of healthcare professionals taking this course, for credit, from NurseCe4Less.com. The information is designed to assist healthcare professionals, including nurses, in addressing issues associated with healthcare. 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