Ch1: Cancer: An Overview 2024 PDF

Ch1: Cancer: An Overview Radiation Therapy Ahmed M.A. Abuali An Najah National University Biophysics and Medical Imaging Department 2024 Ahmed M.A Abuali 1 ...

Ch1: Cancer: An Overview Radiation Therapy Ahmed M.A. Abuali An Najah National University Biophysics and Medical Imaging Department 2024 Ahmed M.A Abuali 1  Introduction Radiation therapy is the medical specialty that uses ionizing radiation to treat cancer and some benign diseases. The goal of radiation therapy is to deliver the maximum amount of radiation needed to kill the cancer, while sparing normal surrounding tissue. To accomplish this goal, radiation therapy relies heavily on physics and biological sciences, including radiobiology and computer science. The technological and medical advances during the last 20 years have thrust radiation therapy into a new and exciting era, in which the highest level of accuracy and the ability to greatly reduce dose to the normal structures is possible. Ahmed M.A Abuali 2  It is important to remember that although the technology and equipment are advanced and exciting, the focus of radiation is on the person diagnosed with disease. The focus of the radiation therapist remains the patient, providing quality care, educating, making referrals as needed, and making daily assessments. A meaningful, daily connection with the patient is important as any other task the therapist accomplishes. Ahmed M.A Abuali 3  PATIENT PERSPECTIVE Although cancer is often a curable disease, the diagnosis is a life changing event. In studying the various aspects of neoplasia, care providers can easily lose sight of the person behind the disease. The patient must be the focal point of all of the radiation therapist’s actions. The highest level of quality care results from an in-depth knowledge of the disease process: psychosocial issues; patient care; and principles and practices of cancer management, including knowledge of radiation therapy as a treatment option. Ahmed M.A Abuali 4  BIOLOGIC PERSPECTIVE Building on the work of early investigators and aided by technologic advances, researchers are able to diagnose many tumors in extremely early stages. In addition, scientists are able to examine the deoxyribonucleic acid (DNA) of cells obtained through biopsy to determine mechanisms causing uncontrolled growth. Although it is true that technology and knowledge about cancer has increased during the past decades, there is still much to be learned. Ahmed M.A Abuali 5  Theory of Cancer Initiation Tumors are the result of abnormal cellular proliferation. This can occur because the process by which cellular differentiation takes place is abnormal or because a normally non-dividing, mature cell begins to proliferate. Cellular differentiation occurs when a cell undergoes mitosis and divides into daughter cells. These cells continue to divide and differentiate until a mature cell with a specific function results. When this process is disrupted, the daughter cells may continue to divide with no resulting mature cell, thus causing abnormal cellular proliferation. Ahmed M.A Abuali 6  Theory of Cancer Initiation The cause of this cellular dysfunction has been the subject of research for many years. Researchers now know that cancer is a disease of the genes. Normal somatic cells (nonreproductive cells) contain genes that promote growth and genes that suppress growth, both of which are important to control the growth of a cell. In a tumor cell, this counterbalanced regulation is missing. Ahmed M.A Abuali 7  Theory of Cancer Initiation Mutations occurring in genes that promote or suppress growth are implicated in the deregulation of cellular growth. Mutations in genes that promote growth force the proliferation of cells, whereas mutations to the genes that suppress growth allow unrestrained cellular growth. For many tumors, both mutations may be required for progression to full malignancy Ahmed M.A Abuali 8  Theory of Cancer Initiation The terms for the genes involved in the cancer process are proto-oncogenes, oncogenes, and antioncogenes. Proto-oncogenes are the normal genes that play a part in controlling normal growth and differentiation. These genes are the precursors of oncogenes (gene that regulates the development and growth of cancerous tissues.), or cancer genes. Ahmed M.A Abuali 9  Theory of Cancer Initiation The conversion of proto-oncogenes to oncogenes can occur through point mutations, translocations, and gene amplification, all of which are DNA mutations. Oncogenes are implicated in the abnormal proliferation of cells. Antioncogenes are also called tumor-suppressor genes. These are the genes that tell cells to stop multiplying. Inactivation of antioncogenes allows the malignant process to flourish Ahmed M.A Abuali 10  Theory of Cancer Initiation What causes these mutations to occur? For somatic cells, exposure to carcinogens such as certain viruses, sunlight, radiation, and cigarette smoke is implicated. In some situations, such as the familial form of retinoblastoma, gene mutations are passed down through generations. Random mutations that occur during normal cellular replication can also lead to unregulated cellular growth. Ahmed M.A Abuali 11  Theory of Cancer Initiation Researchers have identified several gene mutations, including the gene implicated in the familial form of breast cancer. With the use of gene mapping and advanced technology, study in this area will continue. To understand the principles of cancer treatment, a review of the cell cycle and an overview of tumor growth are necessary. Ahmed M.A Abuali 12  Tumor Growth When all cells operate normally, there is a balance between cells that are dying and the replication of cells. Malignant cells possess damaged genetic material, resulting in increased cell death. While tumor growth larger, the blood, oxygen and nutrient supply is inadequate, creating areas of necrosis or dead tissue. Treatment reduces the # of cells. Cells that are rapidly dividing are more sensitive to the effects of radiation and chemotherapy. Ahmed M.A Abuali 13  Tumor Classification Classified by anatomic site, cell of origin, and biologic behavior. Tumors can originate from any cell. Well-differentiated tumors (closely resemble cell of origin) can be easily classified according to histology. Undifferentiated tumors don’t resemble normal cells, so classification is more difficult. Anaplastic = Undifferentiated = primitive appearance Tumors are divided into: Benign , or Malignant Ahmed M.A Abuali 14 Ahmed M.A Abuali 15  Tumor Classification Benign: well differentiated, do not metastasize or invade surrounding normal tissue. Benign: oftenly encapsulated, slow growing. Benign: little harm on host, (some harmfull = location, Brain). Benign tumors may be noted by the suffix -oma, which is to the term indicating the cell of origin. For example, a chondroma is a benign tumor of the cartilage. Although this is a general rule, there are malignant tumors, such as melanoma, that end with the same suffix but are malignant Ahmed M.A Abuali 16  Tumor Classification Malignant tumors often invade and destroy normal surrounding tissue and, if left untreated, can cause the death of the host. A well or moderately well differentiated malignant tumor cell will resemble the cell from which it originated. A poorly differentiated cell will have very few of the characteristics of the originating cell, and an undifferentiated cell will have no characteristics of the original cell. They have the ability to metastasize, or spread to a site in the body distant from the primary site. Ahmed M.A Abuali 17  Tumor Classification Tumors arising from mesenchymal cells are known as sarcomas. These cells include connective tissue such as cartilage and bone. An example is a chondrosarcoma or a sarcoma of the cartilage. Although blood and lymphatics are mesenchymal tissues, they are classified separately as leukemias and lymphomas. Ahmed M.A Abuali 18  Tumor Classification Carcinomas are tumors that originate from the epithelium. These include all the tissues that cover a surface or line a cavity. For example, the aerodigestive tract is lined with squamous cell epithelium. Tumors originating from the lining are called squamous cell carcinoma of the primary site. An example is squamous cell carcinoma of the lung. Ahmed M.A Abuali 19  Epithelial cells that are glandular are called adenocarcinoma. An example is the tissue lining the stomach. A tumor originating in the cells of this lining is called adenocarcinoma of the stomach Ahmed M.A Abuali 20 Ahmed M.A Abuali 21  ETIOLOGY AND EPIDEMIOLOGY Etiology is the study of the cause of disease. Although the cause of cancer is unknown, many carcinogenic agents and genetic factors have been identified and are called risk factors. Experts use this information, as they have done with tobacco use, to establish prevention programs and identify high-risk individuals. Ahmed M.A Abuali 22  ETIOLOGY Etiologic and epidemiologic information is helpful in determining screening tests for early detection, producing patient education programs, and identifying target populations. An example is the set of guidelines for screening mammograms to detect breast cancer in its early stages. Ahmed M.A Abuali 23  Epidemiology Epidemiology is the study of disease incidence. National databases provide statistical information about patterns of cancer occurrence and death rates. With this information, researchers can determine the incidence of cancer occurrence in a population for factors such as age, gender, race, and geographic location. Researchers can also determine which specific type of cancer affects which specific group of people. Ahmed M.A Abuali 24  DETECTION AND DIAGNOSIS Early detection and diagnosis are keys to the successful treatment of cancer. Generally, the earlier a tumor is discovered, the lower the chance of metastasis or spread to other parts of the body and the better the chance for cure. For some tumors, such as carcinoma of the larynx, early symptoms such as a very hoarse voice cause the patient to seek medical care early in the course of the disease. As a result, the cure rate for early stage glottic (or true vocal cord) tumors is extremely high. Ahmed M.A Abuali 25  DETECTION AND DIAGNOSIS Cancer of the ovary, however, is associated with vague symptoms such as bloating, upset stomach or abdominal discomfort that could be the result of a number of medical problems. Consequently, a diagnosis is often made late in the course of the disease. Low cure rates for ovarian cancer reflect the results of late diagnosis. Ahmed M.A Abuali 26  Screening Examinations To identify cancer in its earliest stages (before symptoms appear and while the chance of cure is greatest), screening tests are performed. Examples include the Pap smear for cervical cancer, fecal occult blood testing or colonoscopy for colorectal cancer, and mammograms for breast cancer. Unfortunately, for many cancers, screening examinations are not readily available because of the inaccessibility of the tumor or the high cost in relation to the information yield associated with the tests. Ahmed M.A Abuali 27  Screening Examinations To be useful, screening examinations must be sensitive (ability of a test to give a true-positive result) and specific (ability of the test to obtain a true-negative result) for the tumors they identify. If an examination is sensitive, it can identify a tumor in its extremely early stages. A sensitive test will NOT result in false-negative findings. A false-negative finding would be one where it appears that there is no cancer present when indeed there is cancer. Ahmed M.A Abuali 28  Screening Examinations For example, a Pap smear is sensitive because it can help detect carcinoma of the cervix before the disease becomes invasive. If a test is specific, it can identify a particular type of cancer. For example, a prostate-specific antigen is used specifically for prostate cancer. Unfortunately, it results in a number of false-positive readings. Ahmed M.A Abuali 29  Screening Examinations Screening tests may yield false-positive or false-negative readings. A false-positive reading indicates disease when in reality none is present. In these cases, patients may undergo additional unnecessary, morbid and costly screening exams or treatments. Ahmed M.A Abuali 30  Screening Examinations A false-negative reading is the reverse; the test indicates no disease when in fact the disease is present. In these cases, a patient does not have needed treatment until later in the disease trajectory. The perfect scenario is to have a screening exam that is both very sensitive and specific. The cost of the screening examination often limits its use to all but extremely high-risk populations. Ahmed M.A Abuali 31  Work-up Components After a tumor is suspected, a work-up, or series of diagnostic examinations, begins. The purpose of the work-up is to determine the general health status of the patient and to collect as much information about the tumor as possible. To treat the patient effectively, the physician must know the type, location, and size of the tumor; the degree the tumor has invaded normal tissue; the presence or absence of spread to distant sites; the lymph node involvement if any; and amenability to specific treatment regimens. Ahmed M.A Abuali 32  Work-up Components The work-up depends on the type of cancer suspected and the symptoms experienced by the patient. The work-up for a suspected lung tumor is different than that for a suspected prostate tumor. The same questions are answered, but because the two tumors are extremely different, the tests are based on the specific tumor characteristics. Additionally, the work-up for an early stage tumor will be different from later stage disease. Ahmed M.A Abuali 33  Work-up Components With advancing technology, more information is available to the physician than ever before. Much of the guesswork is eliminated with the use of ultrasound, CT, MRI, and positron emission tomography (PET) so treatment volumes can include only areas of known disease while limiting dose to the normal tissue, thereby producing a more effective treatment with fewer short term and chronic treatment side effects. Ahmed M.A Abuali 34  Staging Tumor staging is a means of defining the tumor size and extension at the time of diagnosis and is important for many reasons. Tumor staging provides a means of communication about tumors, helps in determining the best treatment, aids in predicting prognosis, and provides a means for continuing research. Ahmed M.A Abuali 35  Staging A common staging system adopted by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC) is the TNM system. The T category defines the size or extent of the primary tumor and is assigned numbers 1 through 4 or x. A T1 tumor is small and/or confined to a small area, whereas a T4 tumor is extremely large and/or extends into other tissues. The x indicates that there was an inability to obtain information necessary to make a determination. Ahmed M.A Abuali 36  Staging N designates the status of lymph nodes and the extent of lymph node involvement. A 0-through-4 or x designation exists depending on the extent of involvement, with N0 indicating that no positive nodes are present. N1 indicates positive nodes close to the site of the primary tumor, whereas N4 indicates positive nodes at more distant nodal sites. Nx indicates that the nodal status was not assessed. Not all cancers have the designation of N1 through N4. Ahmed M.A Abuali 37  Staging M is the category that defines the presence and extent of metastasis. Again, the M category is generally categorized as 0, 1, or x depending on the extent of metastatic disease. The designation M0 indicates no evidence of metastatic disease was found, whereas M1 indicates disease distant from the primary tumor. Mx indicates that the presence or absence of metastasis was not assessed. Specific tumors with a detailed staging criteria may have an expanded M designation Ahmed M.A Abuali 38 Ahmed M.A Abuali 39  Staging Although the TNM system is widely used, numerous staging systems exist that more accurately detail important tumor characteristics for prognostic and treatment information. For example, the International Federation of Gynecology and Obstetrics (FIGO) system is more commonly used in the staging of gynecologic tumors. Ahmed M.A Abuali 40  Surgical/Pathologic Staging Surgical/pathologic staging offers the most accurate information about the tumor and the extent of disease spread. Although staging can be performed clinically, or without the use of invasive procedures, the status of the lymph nodes and micrometastatic spread would remain in question. During surgical staging, the physician has the opportunity to perform a biopsy of suspicious-looking tissue, obtain a sample of lymph nodes for microscopic examination, and observe the tumor and surrounding tissues and organs. Ahmed M.A Abuali 41  Surgical/Pathologic Staging Ovarian disease may be staged surgically through the use of an intraoperative examination, or surgical exploration of the abdomen, because these tumors often spread by seeding into the abdomen. During the procedure, the primary tumor site is identified, tumor is removed, suspicious areas are biopsied, and fluid is introduced into the abdominal cavity to be removed and examined for cancer cells. Ahmed M.A Abuali 42  Surgical/Pathologic Staging The amount of tumor left behind following the surgery provides important treatment and prognostic information. The greater the amount of information obtained about the tumor, the more accurate the staging is likely to be, which results in more effective treatment. Accurate staging is also able to limit aggressive treatment to only those patients who will benefit. Ahmed M.A Abuali 43  Surgical/Pathologic Staging With the ability to look at a tumor’s cellular DNA, a physician has even more information available to determine, within a tumor type, which tumor is more sensitive to a particular treatment and which tumor has a greater chance of recurrence. Tumor cell DNA examination is standard practice for a variety of cancers and the staging has changed to include DNA characteristics, as well as clinical factors. For example, with breast cancer, overexpression of HER2/neu protooncogene or BRCA1 or BRCA2 will influence the overall treatment plan. Ahmed M.A Abuali 44  Grade Provides information about tumor aggressiveness and is based on the degree of differentiation. Differentiation is divided into four categories: well differentiated, moderately well differentiated, poorly differentiated and undifferentiated or anaplastic. Cancer cells that have the most characteristics of the original cell are well and moderately well differentiated. Cells in which the original cell is barely or not distinguishable are poorly differentiated or undifferentiated. Degree of differentiation is determined only by examination of cells obtained through biopsy under a microscope Ahmed M.A Abuali 45  TREATMENT OPTIONS Cancer treatment demands a multidisciplinary approach. Tumor boards were established so that cancer specialists can work together to review information about newly diagnosed tumors and devise effective treatment plans. Participants of a tumor board can include surgeons, radiation oncologists, medical oncologists, radiologists, pathologists, social workers, plastic surgeons, and other medical personnel. All of these individuals play key roles in developing a treatment plan that effectively treats the tumor while helping the patient maintain a high quality of life Ahmed M.A Abuali 46 Ahmed M.A Abuali 47