Understanding Hodgkin Lymphoma

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2 Understanding Hodgkin Lymphoma A Guide For Patients, Survivors, and Loved Ones Fourth Edition This guide is an educational resource compiled by the Lymphoma Research Foundation (LRF) that provides general information on adult Hodgkin lymphoma. Publication of this information is not intended to take the place of medical care or the advice of a patient s doctor. Patients are strongly encouraged to talk to their doctors for complete information on how their disease should be diagnosed, treated, and followed. Before starting treatment, patients should discuss the potential benefits and side effects of cancer therapy. National Headquarters 115 Broadway, Suite 1301 New York, NY (212) phone (212) fax Helpline: (800) ; [email protected] Website: [email protected] This patient guide is supported through unrestricted educational grants from: 2012 Lymphoma Research Foundation. Information contained herein is the property of the Lymphoma Research Foundation (LRF). Any portion may be reprinted or reproduced provided that LRF is acknowledged to be the source.

3 ACKNOWLEDGMENTS The Lymphoma Research Foundation wishes to acknowledge those individuals listed below who have given generously of their time and expertise. We thank them for their contributions, editorial wisdom, and advice, which have truly enhanced this publication. The review committee guided the content and development of this publication. Without their dedication and efforts, this publication would not have been possible. We hope those in the lymphoma community will now be better informed and have a better understanding of their illness because of the gracious efforts of those involved in the planning and execution of this comprehensive disease guide. Review Committee Ranjana Advani, MD, Stanford University Medical Center Nancy L. Bartlett, MD, Washington University School of Medicine Sven de Vos, MD, PhD, UCLA s Jonsson Comprehensive Cancer Center Randy Gascoyne, MD, FRCPC, British Columbia Cancer Agency David J. Straus, MD, Memorial Sloan-Kettering Cancer Center Anas Younes, MD, The University of Texas, MD Anderson Cancer Center ii Understanding Hodgkin Lymphoma

4 TABLE OF C ONTENTS Introduction...1 Part 1 Learning the Basics...2 Chapter 1: Understanding Hodgkin Lymphoma...2 Chapter 2: Seeking Medical Help...12 Chapter 3: Getting a Diagnosis...15 Chapter 4: Work-up Before Treatment Can Begin...21 Part 2 Treatment of Hodgkin Lymphoma...27 Chapter 5: What You Should Know Before Starting Treatment...27 Chapter 6: Treatments for Hodgkin Lymphoma...40 Part 3 Side Effects and Living With Cancer...59 Chapter 7: Common Treatment Side Effects...59 Chapter 8: Managing Your Life During and After Treatment...77 Part 4 Clinical Trials and Advances in Treatment..82 Chapter 9: Overview of Clinical Trials...82 Chapter 10: Advances in Treatment of Patients With Hodgkin Lymphoma...87 About the Lymphoma Research Foundation...89 Understanding Hodgkin Lymphoma iii

5 I NTRODUCTION The purpose of this booklet is to help patients with Hodgkin lymphoma become active participants in their healthcare decisions. Chapters in this book address different issues faced by these patients, including: what to expect during diagnosis, work-up, and treatment; how to cope with treatment side effects; and what questions to ask doctors. 1 Understanding Hodgkin Lymphoma

6 Part 1 Learning the Basics Chapter 1: Understanding Hodgkin Lymphoma Hodgkin lymphoma (HL) is a type of cancer that affects specialized white blood cells called lymphocytes. Lymphocytes work together with other cells in the immune system to defend the body against invasion by bacteria, viruses, parasites, and other foreign substances. Lymphocytes travel around the body in blood vessels and in a separate network of vessels called the lymphatic system. Part 1 The sections in this chapter will explain these and other terms that will help you understand HL and how it affects a person s health. A better understanding of the disease will help patients take a more active role in deciding the course of their treatment. What is cancer? Cancer is a group of diseases that develop when abnormal cells gain the ability to divide abnormally and to spread to areas in the body where they are not normally found. Your body is made up of many different types of specialized cells that are organized in tissues and organs to perform all the different tasks needed to stay healthy. To keep things running smoothly, the cells in your body grow, work, and divide in a very controlled fashion. All of these cells also have a limited lifespan. Normally, a self-destruct mechanism is triggered when a cell becomes too old or when it stops working properly. However, sometimes damage to the genetic material (DNA) of a cell gives it the ability to override this self-destruct mechanism, allowing these abnormal cells to live longer than normal. Unless the body s immune system gets rid of them, these abnormal cells can multiply and cause cancer. Learning the Basics 2

7 HOW CANCER FORMS INSIDE THE BODY Abnormal Cells Evade the Immune System Abnormal Cells Multiply (Cancer) Tumors May Form (Groups of Abnormal Cells) Most cancers are named after the organ or cell type of origin. For example, a cancer that started in the pancreas is called pancreatic cancer and a cancer that started in lymphocytes is called a lymphoma. 3 Understanding Hodgkin Lymphoma

8 Why is there no single cure for cancer? Cancer refers to a large group of very complicated diseases. A tricky aspect of cancer is that there are many different ways for a cell to become abnormal enough to develop into a cancer cell. Because of this, the path taken by a liver cell to become a cancerous liver cell is quite different from that taken by a lymphocyte to become HL. This is why a treatment that works against one type of cancer may not necessarily work against another. There are also smaller, but still important, differences in the cancer cells found in different patients diagnosed with the same type of cancer. Because of this, a treatment that may work very well in one patient may not have the same positive effect in another. These are some of the reasons why most cancers are much harder to treat or prevent than, for example, bacterial or fungal infections, which typically are caused by a single type of organism. Part 1 What is the lymphatic system? As shown in the picture on page 5, the lymphatic system is a circulatory system that is made up of a spidery network of thin tubes called lymph vessels. Similar to blood vessels, lymph vessels branch out into all tissues of the body. While people can clearly see blood vessels, especially at their wrists and on the top of their hand, the lymph vessels are invisible to the naked eye. Learning the Basics 4

9 ANATOMY OF THE IMMUNE SYSTEM The immune system is the body s defense against disease. Tonsil Thymus Lymph nodes Diaphragm Spleen Lymph vessels 5 Understanding Hodgkin Lymphoma

10 Lymph vessels carry lymph, a type of liquid that contains lymphocytes. Within this huge network of vessels are groups of small, bean-shaped organs called lymph nodes. Thousands of lymph nodes are found throughout the body, including the elbows, neck, armpits, chest, abdomen, and groin. Lymph fluid flows through lymph nodes and specialized lymph tissues such as the spleen, tonsils, bone marrow, and thymus gland. Lymph nodes filter lymph fluid, removing bacteria, viruses, and other foreign substances from the body. If a large number of foreign substances are filtered through a node or series of nodes, swelling may occur and the nodes may become tender to the touch. Most swollen nodes are a reaction to infection and are not cancerous. Part 1 What is a lymphoma? A lymphoma is a cancer that affects lymphocytes, a type of white blood cell. Lymphocytes travel through the blood and lymphatic system to defend the body against foreign invaders like bacteria and viruses. There are 2 major categories of lymphomas: Hodgkin lymphoma (HL) and non-hodgkin lymphoma (NHL). NHL is approximately 8 times more common than HL; according to the American Cancer Society, each year in the United States approximately 9,000 adults are diagnosed with HL and over 70,000 with NHL. Both of these major categories of lymphoma are further subdivided into several types that are different in the way they develop and spread, and in how affected patients are treated. Lymphomas usually develop when a change, or mutation, occurs within a lymphocyte, causing the abnormal cell to replicate faster than, or live longer than, a normal lymphocyte. Like normal lymphocytes, cancerous lymphocytes can travel through the blood and lymphatic system and spread and grow in many parts of the body, including the lymph nodes, spleen, bone marrow, and other organs. In advanced stages, most types of HL are found throughout the body by the time a patient is diagnosed with the disease. Learning the Basics 6

11 What is Hodgkin lymphoma? HL (previously called Hodgkin s disease) is a type of cancer that starts in lymphocytes. HL is named after Dr. Thomas Hodgkin, a British physician who first described the disease in Both children and adults can develop HL; the disease is most common in younger adults aged and older adults aged 55 and older. As a result of advances in the diagnosis and treatment of the disease, over 80% of patients with HL are cured. How does Hodgkin lymphoma develop? HL develops when a lymphocyte (usually a type of lymphocyte called a B cell) becomes abnormal (cancerous). These abnormal cells are called Reed-Sternberg (R-S) cells, named after the 2 scientists, Dorothy Reed and Carl Sternberg, who provided the first definitive microscopic descriptions of HL. Most people with HL have R-S cells, although other abnormal cell types may also be present. R-S cells are the defining cells of HL, although they constitute only a small fraction of the overall tumor mass, and they are not dividing cells. R-S cells produce factors that attract many inflammatory cells that make up most of the overall tumor burden. Due to this circumstance, HL initially was not recognized as a cancer but thought of as an infection. 7 Understanding Hodgkin Lymphoma

12 A REED-STERNBERG CELL Part 1 Reed-Sternberg cell Normal lymphocyte Having R-S cells alone does not necessarily mean that a person has HL. To confirm a diagnosis, the lymphatic tissue sample must also contain other cells and features that are characteristic of HL. To help make the diagnosis, a lymphoma pathologist (a doctor specialized in recognizing lymphoid cancers by examining tissues and organs under a microscope) will use tests that look for cell surface markers (antigens) that identify specific cell types of HL, and may also use more sophisticated molecular tests to help secure a confident diagnosis. HL usually starts in the lymph nodes and may be first noticed in the neck, above or below the collarbone, under the arms, or in the chest. Because lymph tissues all over the body are connected, abnormal (cancerous) lymphocytes can circulate in the lymphatic vessels, causing the lymphoma to spread from one lymph node to another throughout the body. HL can also spread to other areas and organs Learning the Basics 8

13 outside the lymph system. Unlike the more common NHL, HL tends to spread sequentially from one group of lymph nodes to the next, rarely skipping lymph nodes; this is a characteristic attribute of this form of lymphoid cancer. What are the most common types of Hodgkin lymphoma? The different types and subtypes of HL are distinguished according to what they look like under a microscope. The type of tumor a patient has may affect the choice of treatment. The 2 main types of HL are: n Classical HL, which affects 95% of patients diagnosed with HL in developed countries. n Nodular lymphocyte predominant HL. Classical HL (CHL) is subdivided into the following 4 different subtypes: Nodular Sclerosis CHL Mixed Cellularity CHL n This is the most common subtype of HL, affecting between 60-80% of patients with the disease. n Under the microscope, the involved lymph nodes often contain prominent scar tissue leading to the name nodular sclerosis (sclerosis means scarring). n The disease is equally common in men and women, and it usually affects teenagers and young adults. n Most patients are cured with current treatments. n This type of CHL affects 15-30% of patients with HL and is found more commonly in men than women. n Under the microscope, the lymph nodes contain many R-S cells mixed with many other types of cells. n This disease primarily affects older adults. n More extensive disease is usually present by the time patients with this subtype are diagnosed. 9 Understanding Hodgkin Lymphoma

14 Lymphocyte- Rich CHL n This subtype of CHL occurs in 5% of all patients diagnosed with HL. n Under the microscope, this subtype shows many normal lymphocytes and very few abnormal cells and R-S cells. n This disease is usually diagnosed at an early stage in adults and has a low rate of relapse or recurrence. Part 1 Lymphocyte- Depleted CHL n This is the least common form of HL, accounting for fewer than 5% of all patients diagnosed with the disease. n Under the microscope, there are very few normal lymphocytes and many R-S cells. n This is an aggressive lymphoma that is usually not diagnosed until the disease is widespread. Nodular lymphocyte predominant HL is rare, affecting 5-10% of patients diagnosed with HL. It affects more men than women and is usually diagnosed in people under 35. This subtype is often found in the neck lymph nodes, is usually diagnosed at an early stage, and it is not very aggressive (it grows slowly). In many ways, this form of HL is similar to low-grade (indolent) B-cell NHL. Why do some people develop Hodgkin lymphoma? The reasons why people develop HL are not well understood. However, scientists have found that people with certain characteristics have a higher risk of developing HL compared with people who do not have these characteristics. The characteristics that make a person possibly more susceptible to developing any type of disease are called risk factors. Having 1 or more of these risk factors does not mean a person will develop HL. In fact, most people with risk factors never develop the disease and many people diagnosed with HL have never been exposed to clearly identifiable risk factors. Learning the Basics 10

15 Known risk factors for HL include: Age Family History Sex Infection by Certain Viruses Weakened Immune System n People who are years or over 55 years have a higher risk of developing HL than people in other age groups. n People with a family history of the disease, especially among first-degree relatives (parent, brother, or sister), have a higher risk of developing the disease compared with people who do not have first-degree relatives with HL; siblings of patients with HL have a 3- to 7-fold increased risk of developing this disease, and the risk is higher in identical twins. Because HL is a relatively rare cancer, even with a 3- to 7-fold increase in risk, the chance of a patient s family member developing HL is still very low. n Only 1% of patients with HL have a family history of the disease. n Men have a slightly higher risk than women of developing HL, but more women than men have the nodular sclerosis subtype. n People infected with Epstein-Barr virus (EBV; which causes mononucleosis) or the human immunodeficiency virus (HIV; which causes AIDS) have a higher risk of developing HL compared with people who do not have these infections. n People who have a weakened immune system because of an inherited condition or the use of immunosuppressant drugs to prevent organ transplant rejection have a higher risk of developing HL compared with people who have a healthy immune system. HL cannot be caused by injury or by catching it from someone who has the disease. 11 Understanding Hodgkin Lymphoma

16 Part 1 Learning the Basics Chapter 2: Seeking Medical Help This chapter explains the signs and symptoms of HL and discusses how a doctor determines whether or not a person has the disease. Part 1 A symptom is anything unusual in a normal body function, appearance, or sensation that a patient experiences. During a visit with a healthcare practitioner, patients should report all of their symptoms to their doctor or nurse. Symptoms may indicate the presence of lymphoma or another disease. Signs are anything unusual that doctors or nurses notice when they examine their patients. What are the signs and symptoms of Hodgkin lymphoma? The following are signs and symptoms of HL. Keep in mind that 3 out of 4 people (75%) diagnosed with HL do not have any symptoms, and that none of these are specific to HL exclusively. n Lumps under the skin in the neck, under the arm, or in the groin. These lumps are swollen lymph nodes that are usually not tender or painful. Infections, not lymphomas or other cancer, are the most common reasons for swollen lymph nodes; in these cases the swollen lumps should return to normal size within a few weeks or months after the infection goes away. For patients with HL, these lumps persist, although they may fluctuate in size (i.e., get smaller). Learning the Basics 12

17 n Unexplained intermittent fevers that may last for many days or weeks. n Unexplained itching that grows steadily more severe over time and usually affects the trunk, arms, and legs, but it can also be more localized. n Weight loss (usually by more than 10% of a person s normal weight). n Extreme sweating at night enough to drench sheets. n Lack of energy. n Coughing, shortness of breath, or chest discomfort may be signs of HL in the chest. Having one or more of these symptoms does not mean that a person has HL. These symptoms may be caused by an infection or other conditions (including other cancers). When should a patient seek medical attention? Anyone who has persistent symptoms should see a doctor to make sure that lymphoma or another serious condition is not present. A good rule of thumb is to seek medical attention if any of the previously mentioned symptoms last longer than 2 weeks or sooner depending on their severity and impact on a person s daily life. Many of these symptoms can arise from different causes and need not be cancer. There are not any specific tests that doctors can use to routinely screen patients to see if they have HL. During the visit with the doctor, patients should describe all of their symptoms. The doctor will ask detailed questions about medical history and perform a complete physical examination. During the physical examination, the doctor will: n Check for swollen lymph nodes under the chin, in the neck and tonsil area, above the shoulders, on the elbows, in the armpits, and in the groin. n Examine other parts of the body to see if there is swelling or fluid in the chest or abdomen that may be caused by swollen lymph nodes. 13 Understanding Hodgkin Lymphoma

18 n Examine the abdomen to see whether any internal organs are enlarged. n Ask about any pain experienced. n Look for any weakness or paralysis that may be caused by an enlarged lymph node pressing against nerves or the spinal cord. Part 1 If doctors suspect lymphoma after reviewing the symptoms reported and signs they have uncovered during the examination, they will order other tests to confirm the diagnosis. These tests should include a biopsy and may also include blood tests, chest x-rays and other imaging tests, scans, and a bone marrow evaluation. These tests and procedures are discussed in more detail in the next chapter. Learning the Basics 14

19 Part 1 Learning the Basics Chapter 3: Getting a Diagnosis Doctors need the results of different diagnostic tests to accurately determine whether or not a patient has HL. This chapter explains the purpose of these different tests and describes what to expect during and after these procedures. Cautions About Interpreting Diagnostic Reports n Only a biopsy is definitive. n Tests can be reported as normal even though lymphoma may be present. n Tests may be reported as abnormal even though lymphoma is not present. n Other conditions may mimic HL. n The interpretation of tests, such as imaging studies and scans, can be difficult in some situations and needs to be made in the context of the disease and the patient. n Often, follow-up tests are needed to determine the true significance of previous results; additional biopsies may be needed to clarify the results. n Some patients like to review their written scan reports; when doing so, it is important to carefully review the findings with their doctor. How is Hodgkin lymphoma diagnosed? The only way to be absolutely sure of a diagnosis of HL (or any cancer) is for a doctor to perform an excisional biopsy to remove an entire lymph node or an incisional biopsy to remove a portion of the diseased tissue (see next page, What is a biopsy? ). A pathologist will examine slides containing portions of the biopsy sample under a 15 Understanding Hodgkin Lymphoma

20 microscope to see if it contains the characteristic features of Reed- Sternberg (R-S) cells and to see if the cells are arranged in ways typical of HL. A surgical pathologist is a doctor who specializes in the diagnosis of diseases by studying the cells from a patient s blood, body fluids, and tissue samples. A hematopathologist specializes in the pathology of blood cells, and a lymphoma pathologist specializes in the diagnosis and classification of HLs and NHLs. These doctors are trained to recognize different cell types by looking at the shape and size of cells and how they are grouped inside a tissue. Part 1 A core needle biopsy is sometimes used to establish a primary diagnosis, but is not optimal due to the small size of the biopsy sample. In situations where the site of biopsy is difficult to access, a core needle biopsy may be reasonable for diagnostic purposes (see the chart on the next page). In addition to routine pathology analyses, portions of biopsy samples will be used for other tests to confirm the diagnosis and to more exactly identify the specific subtype of HL. This chapter explains how these tests work and what kind of information they provide. What is a biopsy? A biopsy is a procedure in which a piece of tissue from an area of suspected disease is removed from the body and examined under a microscope. The information provided by this tissue sample is crucial to correctly diagnose the disease and decide on the best course of treatment. Learning the Basics 16

21 The following are the 2 main types of biopsies doctors use for the initial diagnosis of patients with a lymphoma: Excisional or Incisional Biopsy Core Needle Biopsy n This is the preferred type of biopsy to establish an initial diagnosis of lymphoma because it allows for the removal of bigger samples than other biopsy procedures. The larger the sample, the more tissue the pathologist can examine, which improves the accuracy of diagnosis. n In this procedure, a surgeon cuts through the skin to remove an entire lymph node (excisional biopsy) or a large portion of tissue (incisional biopsy). n If the lymph node is close to the skin surface, the procedure can be done under local anesthesia to numb the area. If the lymph node is in the chest or abdomen, the patient is sedated and the surgeon removes the tissue, usually by making a small incision above the sternum (breast bone). n This procedure is used when the lymph nodes are deep in the chest or abdomen or in other locations that are difficult to reach with excisional biopsy, or when there is a medical reason for avoiding an excisional or incisional biopsy. n In this procedure, a large needle is inserted into a lymph node suspected to be cancerous and a small tissue sample is withdrawn. n A needle biopsy can be done under local anesthesia and stitches are usually not required. n Sometimes the material collected may not be adequate for diagnosis and a subsequent excisional or incisional biopsy may be necessary. A fine needle aspirate (FNA) biopsy is, as the name implies, a type of biopsy performed with a very thin needle (smaller than that used for a core needle biopsy). Because of the small needle size, the sample will only contain scattered cells without preserving how the cells are actually arranged in the lymph node. This limited information is not enough for a precise diagnosis. A FNA biopsy is most often used to check for return of the disease (relapse) and is virtually never used for the initial diagnosis. 17 Understanding Hodgkin Lymphoma

22 After a tissue sample has been removed, it is examined by a pathologist. If the pathologist s interpretation of the biopsy is uncertain, the results should be reviewed by a hematopathologist or preferably a lymphoma pathologist because a pathologic diagnosis of lymphoma can sometimes be difficult to make. Arming the medical oncologist or hematologist with an accurate diagnosis on which sound treatment decisions can be made is of paramount importance. Part 1 What questions should a patient ask the doctor before having a biopsy or other diagnostic procedures? Patients diagnosed with a complicated disease will be asked to undergo a variety of procedures for the initial diagnosis and work-up before treatment begins, during the course of treatment, and during the follow-up period. Before patients agree to a procedure, they should make sure that they understand the reasons for the procedure and what will be involved. Here is a list of questions patients may want to ask their doctor. n Why is this procedure necessary? n What will the procedure tell us about my condition? n Can the same information be obtained in another way? n What is involved in doing this procedure? n What are the possible risks, complications, and side effects? n Where will I have the procedure done? n Will I have to do anything to prepare for the procedure? n How long will the procedure take? Will I be awake? Will I feel pain? n How long will it take for me to recover from the procedure? n Should anyone else be present when I have the procedure? n Will I need someone to take me home afterward? n When will I know the results? n When will we talk about the results? n What will be my out-of-pocket costs? Learning the Basics 18

23 What is immunophenotyping? Immunophenotyping is a process used during evaluation of biopsy material to distinguish between different types of cells (for example, between normal lymphocytes and lymphoma cells), by detecting specific molecules (cell markers or antigens ) found on the cell surface. These cell markers are detected using special antibodies grown and chemically modified in the laboratory so that they will change color when they stick to their corresponding markers. IMMUNOPHENOTYPING Antibodies change color upon binding to specific cell markers. Antibody Antigen 19 Understanding Hodgkin Lymphoma

24 This color change is studied under a microscope using immunohistochemistry (IHC) analysis. Immunohistochemistry (IHC) n In this test, thin slices of the biopsy sample (or thin layers of fluid or blood) are placed on slides and treated with sets of antibodies that recognize different markers found in different types of lymphoma cells and normal lymphocytes. n The pathologist examines the slides under a microscope to look for the visible color change that happens when the antibody sticks to the marker. n The pathologist identifies and counts the number of cells that change color (meaning that they are positive for the marker) with each of the different antibodies and uses that information to identify the specific type of lymphoma. Part 1 Learning the Basics 20

25 Part 1 Learning the Basics Chapter 4: Work-up Before Treatment Can Begin After the initial diagnosis of HL, the doctor may order other tests such as blood tests, bone marrow biopsy and aspiration, imaging studies (especially x-ray, CT, and PET scans), and heart and lung function tests. This process is often called the work-up. Some of these work-up studies are needed to see if and how much the disease has spread to other parts of the body. Doctors will use these test results to determine the stage of a patient s disease. Other tests will check how the disease has affected a patient s overall health and major organ functions. Together all of these tests will provide the information needed to help patients and their doctors decide on the course of treatment that will give patients the best chance for curing the disease or putting it into a lasting remission. This chapter will help you understand how HL is staged, the reason for the various tests, how these tests work, and what to expect. How is Hodgkin lymphoma staged? Staging is used to describe how widely the lymphoma has spread in patients with HL. As shown in the following figure, there are 4 main stages of lymphoma, designated by the Roman numerals I through IV. This staging system divides the body in half using the diaphragm, the muscle that divides the chest cavity from the abdominal cavity. 21 Understanding Hodgkin Lymphoma

26 STAGING OF HODGKIN LYMPHOMA Stage II: Two or more lymph node regions near each other One or more lymph nodes and one organ near each other Stage III: Two or more lymph node regions in different parts of the body with or without involvement of a nearby organ or the spleen Stage IV: Widespread disease Multiple organs With or without lymph node involvement Your doctor may also add any of the following single letters to the stage: n n n A if patients have not experienced symptoms such as significant weight loss (more than 10% in 6 months), drenching night sweats, or fevers. B if patients have lost weight (more than 10% in 6 months) and have experienced drenching night sweats or fevers. X if patients have a tumor in the chest that according to a chest x-ray is at least one-third as wide as the chest, or if tumors in other areas that are at least 10 cm (4 inches) wide, it is called bulky disease. Patients with bulky disease usually need more intensive treatment than patients without bulky disease. Learning the Basics 22 Part 1 Stage I: Localized disease Single lymph node region Single organ outside lymph nodes

27 Remember that advanced stages of HL are curable, unlike advanced stages of solid tumor cancers, which are more difficult to treat. What is the purpose of blood tests? Doctors will test a patient s blood to measure the quantity of the different types of cells (red blood cells, white blood cells, and platelets). While HL cells are not found in the blood, blood tests will help doctors determine how advanced the disease is and whether a patient will be able to tolerate certain kinds of treatments. The blood tests will most likely include: a complete blood count (CBC), differential (to measure the relative amounts of different types of white blood cells), platelets, erythrocyte sedimentation rate (ESR), alkaline phosphatase and other liver enzymes, and serum lactate dehydrogenase (LDH). Patients with risk factors for human immunodeficiency virus (HIV) will also be tested for HIV. Prior to therapy, the blood will also be tested for exposure to the hepatitis B virus (HBV). If the patient is a woman of childbearing age, her doctor will also do a pregnancy test because some of the possible treatments may hurt a fetus. The results from these tests will help patients and their doctors decide between different types of treatments. Many of these blood tests will be repeated during the course of treatment to check how the treatment is affecting the patient s body functions. What types of imaging tests may be used? The imaging tests usually recommended for a patient with HL are a chest x-ray and PET/CT scans of the neck, chest, abdomen, and pelvis. The purpose of these tests is to help find areas of the body where there may be cancer, to learn how far the cancer has spread, and later on to check how well the treatment is working. Most of these tests are painless, and no anesthetic is required. 23 Understanding Hodgkin Lymphoma

28 X-ray Computer Tomography (CT) Scan Positron Emission Tomography (PET) Scan n X-rays use radiation to take pictures of areas inside the body. The amount of radiation used in most diagnostic tests is so small that it poses little risk to the patient. n Findings on a chest x-ray may indicate whether the disease is bulky. n A CT scan takes x-rays from many different angles around the body. A computer combines the pictures obtained from these different angles to give a detailed image of organs inside the body. n Patients with HL often have CT scans of the neck, chest, abdomen, and pelvis. These tests are useful in determining how many nodes are involved, how large they are, and whether internal organs are affected by the disease. n The amount of radiation exposure during a CT scan varies depending on the area scanned. Most CT scans confer little risk to the patient, although CT scans of the abdomen and pelvis do add a moderate amount of risk (1 in 500-1,000) to the general lifetime risk of cancer. n Before a CT scan, the patient may be asked to drink a contrast liquid and/or get an intravenous injection of a contrast dye that will more clearly outline abnormal areas that may be present in the body. n PET scans are very important for the initial staging of HL. n To perform the test, radioactive sugar is first injected into the body. Increased uptake of the sugar in areas affected by HL are detected using a positron camera. The amount of radiation used for a PET scan is low and poses little risk to a patient. n PET scans can help determine how much disease is present (staging) and how well it has responded to treatment. n While CT scans show the size of a lymph node, PET scans show if the lymph node is active (still has significant disease). Today, CT and PET scans are often combined into 1 test (integrated PET/CT). Part 1 Learning the Basics 24

29 Magnetic Resonance Imaging (MRI) n Like a CT scan, an MRI takes images from different angles around the body, but an MRI does not use x-rays like a CT scan; instead it uses magnets and radiofrequency waves. MRI is not used routinely for staging, but sometimes can provide useful additional information. n An MRI can provide important information about tissues and organs, particularly the nervous system, that is not available from other imaging techniques. To create a clearer picture, a contrast dye may be injected into a patient s vein. n A doctor may order an MRI to get clear images of the bones, brain, and spinal cord to see if the cancer has spread to these areas. What is a MUGA scan? A MUGA scan (multi-gated acquisition scan) is an imaging test that looks at how well the heart muscle is working. A MUGA scan is done to make sure that the patient s body can withstand treatment with certain lymphoma drugs that may damage the heart in rare cases. MUGA scans may be done when patients are resting or exercising, depending on what their doctor wants to assess. A doctor will most likely order a MUGA scan if he or she is considering treating a patient with the drug doxorubicin (Adriamycin). This test is needed to make sure that the heart is functioning normally because doxorubicin may be associated with cardiac toxicity. A 2-dimensional echocardiogram (ECHO) is sometimes used instead of the MUGA scan to test heart function. Why might a patient need to have a lung function test? Lung function tests are done to make sure that the body can withstand treatment with certain lymphoma drugs that may stress a patient s lung function. Lung function tests are usually needed in patients with HL who will be undergoing treatment with a chemotherapy regimen that contains the drug bleomycin (Blenoxane). Bleomycin can cause lung damage. A doctor may order breathing tests before beginning treatment and at other times during treatment to make sure that a patient s lungs are still working properly. 25 Understanding Hodgkin Lymphoma

30 What is a bone marrow biopsy and aspiration? Once the diagnosis of HL is made, the doctor may order a bone marrow biopsy and aspiration to see if the lymphoma has spread to the bone marrow. The bone marrow is the spongy, soft material found inside our bones. Bone marrow biopsy is recommended for patients with symptoms or stage III or IV disease. The information from this procedure will help the doctor stage the disease. Part 1 What happens during bone marrow biopsy and aspiration? n The patient lies on the exam table, either on a side or on the stomach. n For the aspiration part of this procedure, the doctor cleans and numbs the skin over the hip and inserts a thin hollow needle into the bone. n The doctor uses a syringe to remove a small amount of liquid from the bone marrow. Even with the numbing local anesthetic, this procedure can be painful for a few seconds while the marrow is withdrawn. n For the biopsy part of this procedure (which is usually done right after the aspiration), the doctor inserts a slightly larger needle to take out a small piece of bone and marrow. This procedure may cause mild pain or a pressure sensation. The procedure does not require any stitches. n A pathologist looks at the samples under a microscope to see if there are any signs of HL. Patients who are anxious about the test should talk with their doctor and nurse to see whether taking a calming medication before the procedure would be helpful. Learning the Basics 26

31 Part 2 Treatment of Hodgkin Lymphoma Chapter 5: What You Should Know Before Starting Treatment Getting a cancer diagnosis is an overwhelming experience. It is perfectly normal to be shocked by the diagnosis, anxious about the future, and confused about the medical information and decisions that need to be made. This chapter will help you prepare for the start of treatment by explaining the next steps and providing tips for talking with a patient s doctor about any questions and concerns. First Steps to Take After Receiving a Diagnosis n Take care of yourself (eat, sleep, rest, and exercise). PATIENT TIP n Seek the support of family, friends, and others on whom you trust and rely. n Learn about the disease and treatment options. n Find medical care that meets your needs. n Find emotional and social support. n Understand the cost of care and what your insurance will cover. n Maintain a copy of your medical records (paperwork, test results, and your own notes). Who will plan and carry out the treatment? The treatment of patients with HL is usually overseen by a medical oncologist or hematologist who specializes in the treatment of patients with lymphoma. Depending on the patient s healthcare needs, the doctor may refer him or her to, or work with, other specialists such as a radiation oncologist. The patient s healthcare team will also include other healthcare professionals such as an oncology nurse, nurse practitioner, physician assistant, social worker, and registered dietitian. The healthcare team should work together and communicate with you to plan, carry out, and monitor the treatment. 27 Understanding Hodgkin Lymphoma

32 What is a prognosis? Prognosis is the medical term doctors use for predicting how the disease will progress and the likelihood for recovery. This is often one of the first things that patients ask their doctor. Keep in mind that HL is highly curable. About 80% of all patients with HL will be cured of their disease; that number rises to more than 90% in patients with earlystage disease. Prognosis is usually based on information gathered from hundreds or thousands of other patients who have had the same disease. This statistical information provides doctors with a general idea of what to expect when a patient is diagnosed with a specific type of HL, and also gives guidance on the kinds of treatments that have been most successful in treating that cancer. Part 2 Keep in mind that no two patients are alike and that statistics from large groups of people cannot accurately predict what will happen to a specific patient. The doctor most familiar with the patient s situation is in the best position to help interpret these statistics and understand if and how they may apply to a patient s particular situation. Treatment of Hodgkin Lymphoma 28

33 Patients with classical HL are grouped in the following prognostic categories to help doctors decide on the best course of treatment. Prognosis Stage Risk Factors Early Favorable Stage I or II None Early Unfavorable Stage I or II One or more of the following: n A tumor in the chest larger than onethird of the width of the chest according to a chest x-ray or at least 10 cm (bulky disease). n Cancer in an organ outside the lymphatic system but adjacent to a lymph node containing a tumor. n A high sedimentation rate also called erythrocyte sedimentation rate (ESR), which refers to the distance red blood cells travel in 1 hour in a sample of blood as they settle to the bottom of a test tube; inflammation, infection, cancer, rheumatic disease, and diseases of the blood and bone marrow increase the ESR. n Cancer in 3 or more nodal areas. n The presence of B symptoms (fever, weight loss, or night sweats). Advanced Favorable: Stage III or n Male. 0-1 Risk Factors Stage IV n Age 45 years or older. Intermediate: 2-3 Risk Factors Unfavorable: 4 Risk Factors n Stage IV disease. n Low blood albumin (protein) level (below 4). n Low hemoglobin level (below 10.5). n High white blood cell count (15,000 or higher). n Low lymphocyte count (below 600 or less than 8% of the white blood cell count). 29 Understanding Hodgkin Lymphoma

34 How does having a bulky tumor affect the patient s prognosis? Having a bulky or high-bulk tumor means that the patient has a tumor in the chest that is at least one-third as wide as the chest according to a chest x-ray, or a single mass of tumor tissue greater than 10 centimeters (4 inches) located anywhere. Because of the presence of bulky tumor, the patient will have to be treated more aggressively than a patient who has the same stage of disease but no bulky tumor. Often, but not always, radiation therapy is incorporated into the treatment of patients with bulky tumors. While smaller tumors are usually easier to eliminate than larger tumors, patients with bulky HL also have a high chance of being cured. Part 2 How will we decide what is the best treatment? There are many effective treatment options for patients with HL. To identify which treatments may work best, doctors consider the following: n The type of HL. n The extent of the disease (stage, location, and bulkiness). n Results of blood tests and other lab tests. n The presence or absence of lymphoma symptoms. n A patient s overall health. n A patient s age and medical history. n A patient s preferences. A doctor will discuss the risks, benefits, and side effects associated with the different treatment choices applicable to the patient s particular situation. Share questions and concerns with the doctor so that together you can decide which option is best. Use the following questions to help you make an informed decision. Treatment of Hodgkin Lymphoma 30

35 Questions to Ask Before Treatment Begins n What is my exact diagnosis? May I have a copy of the report from the pathologist? n What is the stage of my disease? Where are the tumors? PATIENT TIP n What are my treatment choices? Which do you recommend for me? Why? n Are new treatments being studied? Would a clinical trial be appropriate for me? n Do I need more than one type of treatment? n What is the goal of treatment? n What are the expected benefits of each type of treatment? How will we know if the treatment is working? What tests will I need to have to check if it works? How often will I need to get tested? n What are the risks and possible side effects of each treatment? Can these side effects be prevented or controlled? n What should I do to take care of myself during treatment? n Are there any late or long-term side effects that I should be aware of? n How long will the treatment last? n What are the chances that the treatment will be successful? n How will the treatment affect my normal activities? n How often will I need a checkup? n How much will the treatment cost? Will my insurance cover it? 31 Understanding Hodgkin Lymphoma

36 When should a patient get a second opinion? Before starting any type of treatment, a patient may consider getting a second opinion especially if some characteristics of the diagnosis are complicated or uncertain. The purpose of the second opinion is not to question the doctor s expertise, but to make sure that the suggested treatment plan is reasonable and optimal for the patient s particular case. Do not be concerned that you will offend your doctor by requesting a second opinion. Most doctors will be supportive and helpful if you tell them that you would like to get a second opinion. Ask the doctor if it would be okay to briefly delay the start of treatment to give extra time to get a second opinion. Keep in mind that some insurance programs require second opinions; others may cover it if a patient or doctor requests it. Part 2 PATIENT TIP Getting a Second Opinion n Some hematologists/oncologists/lymphoma specialists associated with medical schools or cancer centers may provide a consultation and be willing to work together with a local oncologist to provide treatment and follow-up care. n As part of the second opinion, another pathologist must review the tissue and blood samples to confirm the diagnosis. Ask your doctor about finding a pathologist with a lot of experience diagnosing patients with lymphoma. n To get a second opinion, you will have to provide the consulting doctor a complete copy of all medical records, original x-rays, pathology materials, scans, and reports. When you set up the appointment, ask their office for a list of all the materials they will need. It may be useful to keep your own copy of all these records in case you have questions or concerns later on. Treatment of Hodgkin Lymphoma 32

37 To identify lymphoma specialists to contact for a second opinion: n Ask your current doctors, family members, other patients, friends, and coworkers. n Contact the patient referral service at your local hospital and at the nearest hospital associated with a medical school; many hospitals have online directories that can be searched to find a specialist in your area. n Visit the American Society of Clinical Oncology (ASCO) at to search their oncologist database. n Visit the American Society of Hematology (ASH) at to search for hematologists with an interest in lymphoma. n Visit the National Cancer Institute (NCI) at to identify the nearest NCI-designated cancer center and call or visit their website to find out about their lymphoma specialists. n Visit the American Board of Medical Specialists (ABMS) at and click on, Is My Doctor Board Certified to find out if doctors are board certified in a particular specialty. How to find an oncologist and treatment center? A patient s primary care doctor will probably have referred them to a specialist likely a medical oncologist, hematologist, or hematologist/ oncologist. Oncologists are physicians who specialize in diagnosing and treating patients with cancer. Hematologists are physicians who specialize in diagnosing and treating patients with disorders of the blood and lymphatic system. Many physicians are experienced in both areas, and there is some overlap. Before agreeing to treatment by a specific specialist and treatment center, make sure that they will be able to meet all medical and personal needs. Patients should feel comfortable with the healthcare team and the quality of the care they provide. 33 Understanding Hodgkin Lymphoma

38 Here are some questions to ask to select the best medical team: n What are the credentials of the specialist, the other members of the medical team, and the hospital or cancer center? n Is the specialist board certified as a medical oncologist and/or hematologist? Has he or she passed qualifying examinations by the American Board of Internal Medicine to certify competency in these specialties? n How much experience do the specialist and treatment center have in treating patients with cancer in general, and HL in particular? n How many patients with this disease are being treated here now? n Does the specialist and/or center participate in clinical trials? n How much time does the specialist spend on research and how much on the treatment of patients with HL? n Is the specialist a member of the American Society of Clinical Oncology and/or the American Society of Hematology? n Does the clinic or center have modern surgical facilities and diagnostic equipment? n Is the specialist or clinic affiliated with any major medical center or medical school? n What arrangements are made for medical coverage after hours and on weekends, in case of an emergency? n Is my health insurance accepted at this center? Will the office file claims for reimbursement and process the paperwork? n What kind of patient resources does the clinic or cancer center have for patients with my disease? Part 2 Patients enrolled in a managed care program may have limited choices. However, patients have the right to choose another healthcare team if they are not entirely satisfied with their first consultation visit. They should talk with other patients about their experience and ask them if they would recommend their specialist and healthcare team. Also, patients should share their concerns with their primary doctor and ask for a referral to a different specialist if they are not satisfied after their first visit. Treatment of Hodgkin Lymphoma 34

39 How to communicate with the healthcare team Patients can ease their anxieties by establishing open, honest communication with their doctor and nurse regarding their diagnosis, and learning about what the prescribed treatment regimen is, how it works, what tests are involved, and what side effects and complications may be associated with it. A good first step is to write down all questions that come to mind. Before meeting with a doctor or nurse, whether for the first time or for follow-up visits, consider organizing these questions to bring to the visit. Put the 2 or 3 most important questions at the top of your list, since time with doctors or nurses may be limited. But make sure that a member of the medical team reads all of your questions, because they may see some that are more important than you realize. Patients should consider having a family member or close friend accompany them to the doctor s office or clinic to help ask questions and understand and remember answers. A companion could also help by taking notes during the visit. Some patients bring a recording device to record the answers. Check with the patient s doctor before recording any conversations. Most oncology nurses are also very well informed about cancer treatments and are a good source of information on a wide range of topics. Oncology social workers are also available to assist with practical and emotional needs from the time of diagnosis and onwards. Although family members are often very concerned about their loved one and want information concerning his or her care, confidentiality rules prohibit doctors from giving out information to anyone without the patient s expressed permission. For efficiency, designate 1 family member as the family contact. The patient must remember to specifically tell the doctor the identity of the primary family contact. 35 Understanding Hodgkin Lymphoma

40 At home Communicating With Your Doctors n Keep a journal of your symptoms to help you remember the details you want to discuss with your doctor during your next office visit. PATIENT TIP n Make a list of questions that you want to ask your doctor but if the questions are urgent, do not wait for the next visit; call the doctor s office to discuss your concerns. At your next doctor s visit n Bring your symptom journal and list of questions, and discuss them with your doctor or nurse. n Ask a family member or friend to come with you to provide emotional support and take notes. n Do not be afraid to ask questions if you do not understand something. Your doctor will want to know if you are uncertain or confused, and will be happy to explain things to you. n Clarify who should be contacted for specific sorts of questions, or for weekend support. n Ask if members of your healthcare team communicate by . Part 2 n Before leaving the doctor s office, make sure that you understand the next steps in your care. n Ask for written information that you can take home to help you remember what to do, and learn more about your treatment. Treatment of Hodgkin Lymphoma 36

41 What is the purpose of an Advance Healthcare Directive and Appointing a Healthcare Proxy Having an Advance Healthcare Directive (a living will) and appointing a Healthcare Proxy is something that all adults should consider doing regardless of their healthcare status. This is something for everybody to think about, not just people with cancer remember that HL is highly curable but accidents and other unforeseen circumstances can happen anytime. Writing down your wishes for critical medical care in an Advance Healthcare Directive is a way for you to formally tell your doctor, family members, and friends about your healthcare preferences and what special treatments you do or do not want if you were critically ill or injured and unable to make and communicate your own decisions. Besides stating medical care instructions, the Advance Healthcare Directive should also include the name of your Healthcare Proxy, or decision maker. This person should be someone you believe will carry out your wishes if you are unable to do so, including any do not resuscitate (DNR) instructions. Before writing an Advance Healthcare Directive, it is important that you understand patients rights and laws regarding Advance Healthcare Directives in your state. Consulting an attorney can provide the legal information, but patients do not have to use an attorney to write an advance directive. Make sure that your Advance Healthcare Directive includes: n Specific instructions on medical care, including the types of special treatment you do or do not want, such as cardiopulmonary resuscitation (CPR), artificial respiration, drugs to make the heart function, kidney dialysis, artificial feeding, and certain surgical procedures. n Your choice of a healthcare proxy. 37 Understanding Hodgkin Lymphoma

42 For more information about Advance Healthcare Directive guidelines for your state, please visit the Caring Connections website of the National Hospice and Palliative Care Organization, at How to be a self-advocate Being a self-advocate and an active participant in your healthcare can be a positive experience and may help restore any sense of control you may have felt was lost following your diagnosis. All patients should remember that they are partners in their treatment plan. Many patients feel better when they actively participate in their care. Part 2 The first steps in participating in treatment are to ask questions, learn about options, and work closely with the doctor. Patients must be comfortable with their doctor and the approach that they take. If you are not comfortable, you should openly discuss your concerns. Confidence in the medical team often leads to confidence in treatment. If you do not feel that the team is a good match, you should ask for a referral. Questions will likely vary depending on the purpose of the meeting with the oncologist (such as the initial visit to discuss the diagnosis or a routine visit to monitor a remission). Ask for the timing of office visits, treatments, and tests. The doctor can help explain what the tests will look for and define the possible responses and the options for further care depending on treatment response. Although each person is different and each response to therapy is unique, knowing someone who has been through the same treatment and who may have had similar concerns can be a source of great comfort for patients. If you are interested in talking to and learning from people who have had similar experiences, you should ask your oncologist, hematologist, oncology nurse, or the oncology social worker about any support groups in your area. Treatment of Hodgkin Lymphoma 38

43 Before you agree to any tests, you should check with your healthcare team to determine which costs are covered by insurance and which are not. You should also not be afraid to talk to your healthcare team about nonmedical issues, such as transportation, finances, insurance, and childcare. Self-Advocacy n Do not be afraid to ask your doctor or nurses questions about your care. PATIENT TIP n Learn more about your specific lymphoma by asking your doctor for information and visiting reliable websites, such as the Lymphoma Research Foundation at or n Take advantage of counseling, support groups, nutritional counseling, fitness classes, and other services offered at your doctor s office, cancer center, or hospital. n Consider joining the Lymphoma Support Network, a nationwide buddy program that matches patients and caregivers with people who had similar experiences. For information about the program, call (800) or [email protected]. 39 Understanding Hodgkin Lymphoma

44 Part 2 Treatment of Hodgkin Lymphoma Chapter 6: Treatments for Hodgkin Lymphoma In this chapter, you will learn about the most common therapies that are currently used in the treatment of patients with HL. One of the most exciting recent developments is the approval in 2011 of brentuximab vedotin (Adcetris), the first new drug approved for HL in almost 35 years. Brentuximab vedotin is currently approved for the treatment of patients with the following: n Hodgkin lymphoma after failure of autologous stem cell transplant or after failure of at least 2 previous combination chemotherapy regimens in patients who are not candidates for an autologous stem cell transplant. n Systemic anaplastic large cell lymphoma after failure of at least 1 previous combination chemotherapy regimen. Part 2 Brentuximab vedotin is a monoclonal antibody with an attached chemotherapy drug, also known as an immunoconjugate. The drug targets CD30, a molecule found on lymphoma cells, and delivers its attached chemotherapy drug directly to these cells. Keep in mind that new therapies may have been approved by the United States Food and Drug Administration (FDA) since this book went to print. Read Chapter 10 to learn about new agents under investigation. Two additional advances in the last 25 years have dramatically changed the way patients with Hodgkin lymphoma are treated: 1. The elimination of surgical staging laparotomies, in which a patient s spleen was removed to evaluate the extent of disease. This was replaced with noninvasive clinical staging using computerized tomography (CT) and positron emission tomography (PET) scans to capture detailed images of internal organs and spot enlarged lymph nodes. Treatment of Hodgkin Lymphoma 40

45 2. Limiting the use of radiation therapy to subgroups of patients who require it, and reducing exposure to radiation therapy in patients who require it by decreasing the dose of radiation and the size of the field of radiation (the amount of body radiated). What words do doctors use to describe the outcome of treatment? Primary Therapy Complete Remission (CR) Cure Disease Progression Partial Remission (PR) Improvement Stable Disease Refractory Disease Relapse This is the first therapy that a patient receives. The choice of primary therapy depends on the pathologic characteristics of the disease, including the factors described previously in this booklet. This term is used when all signs of the lymphoma have disappeared after treatment. This does not mean that the cancer is completely cured; it means that the symptoms have disappeared and the lymphoma cannot be detected using current tests. If this response is maintained for a long period, it is called a durable remission. This word is cautiously used by doctors when there are no signs of the lymphoma reappearing after many years of continuous, complete remission. The term is most often applied to diffuse large B-cell lymphoma or Hodgkin lymphoma. This term means that the disease has worsened or the tumor has grown during therapy. Other terms used to describe this are treatment resistance or resistant disease. This term is used if the lymphoma has responded to treatment and shrunk to less than one-half of its original size. This term is used if the tumor has shrunk following therapy but is still more than one-half of its original size. This term means that the disease has not gotten worse or better following therapy (the tumor has not grown or shrunk), but has stayed about the same size. This refers to a cancer that is resistant to treatment (meaning that it has not disappeared after treatment). This term refers to disease that reappears or grows again after a period of remission. 41 Understanding Hodgkin Lymphoma

46 What types of treatments are used in patients with classical Hodgkin lymphoma? There are 3 general types of therapies for patients with classical HL: n Radiation therapy, which uses high-energy radiation to kill cancer cells. n Chemotherapy, which affects general cell growth and division. n Biological therapy, which works with the body s normal functions (such as the immune system) to fight cancer. These therapy types are described in detail throughout the chapter. Part 2 Most people treated for HL receive some form of chemotherapy and sometimes radiation therapy as their frontline treatment. Bone marrow or stem cell transplantation is typically used in the relapsed or refractory setting. Surgery is used to obtain a biopsy for diagnostic purposes, but it is not a treatment or cure for HL. Although the cure rate in HL is already high, researchers continue to look for ways to treat the small minority of patients whose disease is resistant (refractory) to treatment. For the small number of patients who relapse, alternative therapies, such as stem cell transplantation, may cure the cancer. Ongoing research also continues to find ways to refine currently available treatments by limiting their toxicity and potential for causing secondary illnesses. Better targeted drugs that do not cause such damaging side effects are also being pursued. Treatment of Hodgkin Lymphoma 42

47 This chart shows how different types of classical HL are usually treated. PET/CT scans are often used after several cycles of treatment to determine how many more cycles of treatment are needed. Stage/Type of Lymphoma Stages IA and IIA Stages I and II, Bulky Disease Stages III and IV Resistant Disease or Recurrent or Relapsed Disease Commonly Used Treatment(s) n Chemotherapy followed by radiation therapy to the initial site of disease (involved field radiation therapy, IFRT). n 4-6 cycles of chemotherapy alone. n For patients who do not respond to treatment, high-dose chemotherapy (possibly with radiation therapy) followed by stem cell transplantation. n 4-6 cycles of chemotherapy usually followed by IFRT. n Chemotherapy alone (typically 6 cycles). n For patients who do not respond to treatment, high-dose chemotherapy (possibly with radiation therapy) followed by stem cell transplantation. n Chemotherapy alone (typically 6 cycles), with possible addition of radiation therapy for patients with bulky disease. More intensive chemotherapy may be used if patients have unfavorable features as described earlier. n For patients who do not respond to treatment, high-dose chemotherapy (possibly with radiation therapy) followed by stem cell transplantation. n Clinical trial. n High-dose chemotherapy followed by autologous or allogeneic stem cell transplantation. n For patients ineligible for transplantation: Radiation therapy and/or chemotherapy with drugs not previously used. Treatment with the immunoconjugate brentuximab vedotin (Adcetris). 43 Understanding Hodgkin Lymphoma

48 What types of treatments are used in patients with lymphocyte-predominant Hodgkin lymphoma? Lymphocyte-predominant HL (LPHL) tends to grow slowly and sometimes causes a late relapse. Patients with early-stage favorable LPHL have a better prognosis than those with classical HL. This chart shows how stages of LPHL are usually treated. Stage/Type of Lymphoma Stages IA and IIA Stages IB and IIB Stages IIIA and IVA Stages IIIB and IVB Recurrent or Relapsed Disease Commonly Used Treatment(s) n Involved field radiation therapy (IFRT) or observation. n IFRT with or without chemotherapy. n Rituximab (Rituxan) with or without chemotherapy with or without IFRT. n Observation. n Chemotherapy with or without radiation therapy. n Rituximab with or without chemotherapy. n Local radiation therapy (palliation only). n Chemotherapy with or without radiation therapy. n Rituximab with or without chemotherapy with or without radiation therapy. n Clinical trial. n Observation if recurrence is limited and there are no symptoms. n Chemotherapy or rituximab with or without chemotherapy. Part 2 In some cases HL can transform into a more aggressive type of NHL. Rapid growth of 1 or more lymph nodes is a clear indication for a biopsy to see if such a transformation has occurred. If transformation occurs, treatment of the resulting NHL will be necessary. If a patient experiences recurrent or relapsed transformed NHL (after having completed initial treatment for transformed NHL), then high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation is recommended. Treatment of Hodgkin Lymphoma 44

49 What is chemotherapy? Chemotherapy drugs work against general characteristics of cancer cells such as their tendency to grow and multiply very quickly. Depending on the drug, patients may have to swallow a pill or receive it through a liquid infused directly into a vein (intravenous infusion or IV). During chemotherapy, patients receive the drug, or drugs, 1 or more times a week for 1 or more weeks, followed by a rest period. This regular treatment schedule is called a cycle. The length of the rest period and the number of cycles vary depending on your disease and the type of drugs used. Most patients with HL are treated with combination chemotherapy, meaning 2 or more drugs, instead of a single drug. These chemotherapy drugs are given in a specific order (or schedule) during certain days of each treatment cycle this is called a treatment regimen. The reason to combine drugs is to increase how effectively they kill or damage cancer cells. Oncology nurses are usually responsible for administering the chemotherapy regimen prescribed by the doctor. Most patients receive their chemotherapy in an outpatient clinic, hospital outpatient department, or doctor s office, but sometimes people have to stay in the hospital for their treatment. 45 Understanding Hodgkin Lymphoma

50 Common chemotherapy regimens for classical Hodgkin lymphoma Regimen Abbreviation ABVD Stanford V BEACOPP Generic Name of Drugs (Brand Name) Doxorubicin/hydroxydaunorubicin (Adriamycin, Rubex) Bleomycin (Blenoxane) Vinblastine (Velban) Dacarbazine (DTIC) Doxorubicin/hydroxydaunorubicin (Adriamycin, Rubex) Vinblastine (Velban) Mechlorethamine (Mustargen) Etoposide (VePesid, Etopophos, Toposar) Vincristine (Oncovin, Vincasar PFS) Bleomycin (Blenoxane) Prednisone (Deltasone) Bleomycin (Blenoxane) Etoposide (VePesid, Etopophos, Toposar) Doxorubicin/hydroxydaunorubicin (Adriamycin, Rubex) Cyclophosphamide (Cytoxan) Vincristine (Oncovin, Vincasar PFS) Procarbazine (Matulane) Prednisone (Deltasone) Part 2 Chemotherapy regimens for lymphocyte-predominant Hodgkin lymphoma A variety of chemotherapy regimens can be used for lymphocytepredominant HL. The choice of which regimen to use is based on many factors including patient and physician preference. Communication between the doctor and patient about appropriate treatment is recommended. Observation is also an option for patients with neither symptoms nor bulky disease. Treatment of Hodgkin Lymphoma 46

51 Regimen Abbreviation ABVD CHOP CVP (COP) EPOCH Generic Name of Drugs (Brand Name) Doxorubicin/hydroxydaunorubicin (Adriamycin, Rubex) Bleomycin (Blenoxane) Vinblastine (Velban) Dacarbazine (DTIC) Cyclophosphamide (Cytoxan) Doxorubicin/hydroxydaunorubicin (Adriamycin, Rubex) Vincristine (Oncovin, Vincasar PFS) Prednisone (Deltasone) Cyclophosphamide (Cytoxan) Vincristine (Oncovin, Vincasar PFS Prednisone (Deltasone) Etoposide (VePesid, Etopophos, Toposar) Prednisone (Deltasone) Vincristine (Oncovin, Vincasar PFS) Cyclophosphamide (Cytoxan) Doxorubicin/hydroxydaunorubicin (Adriamycin, Rubex) How is chemotherapy given? Depending on the regimen, patients will be given chemotherapy in pill form, as an injection, or as an intravenous (IV) drip through a vein. To make it easier to give and receive multiple cycles of chemotherapy by IV, the doctor may insert an IV catheter that will stay in place for a few weeks or for the duration the chemotherapy treatment. There are several types of catheters, described in the following chart. Patients should discuss with their doctor what type of catheter, if any, would be best for their particular situation. 47 Understanding Hodgkin Lymphoma

52 Type of Catheter Description Advantages Disadvantages Hickman and Broviac Infusaport or Portacath Peripherally Inserted Central Catheter (PICC line) Consists of 1-3 tubes surgically inserted through the subclavian vein (the vein that runs underneath the collar bone) in the chest wall into a vein. Six to 12 inches of tubing remain outside the skin. A catheter is surgically inserted through the subclavian vein and attached to a small reservoir (port) that lies under the skin. Nothing is visible on the outside except for a bump on the chest. A thin, soft plastic tube is inserted in a large vein in the arm. It makes it easy to draw blood and give drugs using standard needles and without having to pierce the skin. Patients do not have to do anything to care for it; once a month a nurse keeps it clean by flushing with a small amount of injected liquid. A good option for patients who only need to have many short infusions or continuous infusions given in a hospital or at home with a portable pump. Requires proper care to reduce the risk of infection and blockage. The tubes on the outside of the body make it more obvious that a catheter is in place. Patients need training and instructions to learn to clean and take care of the external tubes. The patient must be injected through the skin with a special needle each time it needs to be used. Sometimes it is hard to use it to draw blood samples because of clogging (due to a blood clot). This is more temporary than the other types of catheters. Part 2 Treatment of Hodgkin Lymphoma 48

53 Why is it important to adhere to the chemotherapy treatment schedule? Patients should adhere to their chemotherapy treatment schedule because a full course of chemotherapy works best in the treatment of their disease. In clinical studies, doctors have found that reducing the dose or delaying chemotherapy may decrease the chance of a cure and long-term survival for patients with certain types of lymphomas. Changing the regimen to reduce short-term side effects may actually be harmful in the long run. Some side effects may be unpleasant but tolerable (see Part 3, Side Effects and Living With Cancer ). Other side effects may be serious but can often be anticipated and prevented. It is very important that chemotherapy schedules be maintained to the greatest extent possible. What is radiation therapy? Radiation therapy (also called radiotherapy) uses high-energy x-rays or other types of radiation to kill cancer cells and shrink tumors. Radiation therapy is limited to patients who require it because of the potential long-term toxicities of this treatment. A radiation oncologist will be in charge of your radiation therapy. The part of the body selected to receive the radiation therapy is called the radiation field. In HL, the common areas of the body that are radiated include lymph nodes in the neck, chest, and armpit (mantle field); lymph nodes in the abdomen and possibly spleen; lymph nodes in the pelvis and groin; and in certain circumstances, extended field radiation to both the mantle and upper abdominal fields. Doctors will decide on the type and size of the radiation field depending on the type of tumor and the extent of disease. The total dose of radiation is usually divided and given over 1-6 weeks. During and after the radiation treatment, patients will have to carefully protect the radiation site from the sun. 49 Understanding Hodgkin Lymphoma

54 External beam radiation therapy is the type of radiation therapy used to treat patients with HL. This form of radiation therapy uses a machine outside the body to send electrons, or negatively charged particles, directly to a specific area of the body. The 2 main types of external beam radiation therapy used against HL are: n Involved field radiation therapy (IFRT) In IFRT, the radiation field includes the lymph node regions that are known to contain HL. IFRT is the preferred form of radiation therapy for patients with HL and is usually given after chemotherapy. IFRT is used alone only to treat certain patients with nodular lymphocyte-predominant HL. n Extended field radiation (EFR) In EFR, the radiation field includes the lymph node regions that contain HL and the surrounding normal lymph nodes, in case the disease has spread to levels that cannot yet be detected. EFR is seldom used in patients with classical HL because most are also treated with chemotherapy. EFR is sometimes used as standalone therapy in patients with nodular lymphocyte-predominant HL. Part 2 To prepare for radiation therapy, the healthcare team will precisely mark the patient s body with tiny ink dots (called tattoos) to make sure that only the targeted areas receive radiation. During the day of treatment, they will use lead shields to protect a patient s normal tissues around the radiation field. They use plastic forms, pillows, and rolled blankets to make the patient comfortable and to keep him or her in the proper position. Patients need to lie still on a table beneath a large machine that delivers the radiation painlessly. Once the preparations have been made, it takes only a few minutes to deliver the prescribed dose. Treatment of Hodgkin Lymphoma 50

55 Questions to Ask Before Starting Radiation Therapy n What is the goal of my radiation therapy? PATIENT TIP n How will the radiation be given? n When will treatment begin? When will it end? n How will I feel during the therapy? n What are the side effects of radiation therapy? Is there anything that can be done to prevent them? n Are there any lasting effects? n What can I do to take care of myself during and after the therapy? n How will we know if the radiation therapy is working? n How will the radiation treatment affect my normal activities? What are complementary and alternative remedies? Alternative therapy refers to treatments that are used instead of standard therapy recognized as effective by the medical profession. Currently, there are no viable alternative therapies to conventional cancer care for patients with HL. Patients should not use alternative remedies to replace the standard care suggested by their doctors. Complementary therapy is used in addition to standard medicine to help improve a patient s quality of life and to relieve the effects of chemotherapy, radiation, and surgery. Patients should talk to their doctor before starting any form of complementary therapy because some of these practices can make cancer treatment less effective. 51 Understanding Hodgkin Lymphoma

56 Complementary therapy, also known as integrative medicine, includes the following varied forms of therapy: Mind/Body Therapies Touch Therapies Acupuncture Nutrition n Examples: meditation, guided imagery, self-hypnosis,tai Chi, yoga. n Meditation, guided imagery, and self-hypnosis can help manage stress. n Yoga and Tai Chi minimize stress and improve balance and flexibility. n Examples: massage, reflexology (foot massage), Reiki, etc. n These techniques apply therapeutic pressure to the body to restore a sense of harmony, relaxation, and well-being. n Studies suggest that massage may lessen pain. n Some studies show that acupuncture may relieve pain, nausea, fatigue, hot flashes, and neuropathy (numbness and tingling in the feet and hands) associated with chemotherapy and may help decrease mild depression. n Using ultra-thin needles applied to specific points on the body, acupuncture is safe and painless. Needles used should be disposed of and only used once. n Patients undergoing lymphoma treatment should eat a healthy, well-balanced diet that contains 5-7 servings of fruits and vegetables a day, fish or poultry, and whole grains. Part 2 Treatment of Hodgkin Lymphoma 52

57 What is relapsed or refractory Hodgkin lymphoma? Relapsed HL means that the disease has returned after responding to treatment this is sometimes also called a recurrence. Refractory HL means that the patient s disease no longer responds to a specific treatment. Patients with Hodgkin lymphoma whose disease does not go into complete remission after initial therapy or who relapse after achieving complete remission are often treated with second-line chemotherapy regimens, followed by a stem cell transplant if they respond to second-line treatment. There are many treatment options for patients with relapsed or refractory lymphomas. Exactly what type of treatment is optimal for individual patients with relapsed or refractory lymphoma depends on factors such as the type of lymphoma, age, extent of disease, overall health, and previous therapies received. The preferred treatment for healthy patients with relapsed HL is a chemotherapy regimen that is typically different from that used initially, followed by highdose chemotherapy with autologous stem cell transplantation i.e., transplantation using the patient s own stem cells (in the following pages see, What is stem cell transplantation? ). This chart shows examples of second-line chemotherapy regimens used in patients whose disease has relapsed or recurred after the initial treatment. Regimen Abbreviation ChlVPP C-MOPP Generic Name of Drugs (Brand Name) Chlorambucil (Leukeran) Vinblastine (Velban) Procarbazine (Matulane) Prednisone (Deltasone) Cyclophosphamide (Cytoxan) Vincristine (Oncovin, Vincasar PFS) Procarbazine (Matulane) Prednisone (Deltasone) 53 Understanding Hodgkin Lymphoma

58 DHAP ESHAP GCD GVD ICE IGEV Mini-BEAM MINE VIM-D Dexamethasone (Decadron) Cisplatin (Platinol, Platinol-AQ) High-dose Cytarabine (Cytosar, DepoCyt) Etoposide (VePesid, Etopophos, Toposar) Methylprednisolone (Medrol) High-dose Cytarabine (Cytosar, DepoCyt, Tarabine PFS) Cisplatin (Platinol, Platinol-AQ) Gemcitabine (Gemzar) Carboplatin (Paraplatin) Dexamethasone (Decadron) Gemcitabine (Gemzar) Vinorelbine (Navelbine) Liposomal doxorubicin (Doxil) Ifosfamide (Ifex) Carboplatin (Paraplatin) Etoposide (VePesid, Etopophos, Toposar) Ifosfamide (Ifex) Gemcitabine (Gemzar) Vinorelbine (Navelbine) Prednisone (Deltasone) Carmustine (BCNU, BiCNU) Etoposide (VePesid, Etopophos, Toposar) Cytarabine (Cytosar, DepoCyt, Tarabine PFS) Melphalan (Alkeran) Mesna (Mesnex) Ifosfamide (Ifex) Mitoxantrone (Novantrone) Etoposide (VePesid, Etopophos, Toposar) Etoposide (VePesid, Etopophos, Toposar) Ifosfamide (Ifex) Mitoxantrone (Novantrone) Dexamethasone (Decadron) Part 2 If the disease responds to second-line therapy, patients with classical HL should receive high-dose chemotherapy followed by stem cell transplantation, if eligible. Treatment of Hodgkin Lymphoma 54

59 If the disease does not respond to second-line therapy, patients with classical HL may be treated with radiation therapy, salvage chemotherapy given with or without radiation therapy, or treatment with the immunoconjugate brentuximab vedotin (Adcetris), which is approved for HL after failure of autologous stem cell transplant or after failure of at least 2 previous chemotherapy regimens in patients who are not candidates for autologous stem cell transplant. Patients who do not go into complete remission following treatment or who do not respond to treatment should not lose hope. Complete remission may be achieved following a diagnosis of relapsed or refractory disease. Many patients seek second opinions at any point from diagnosis onward and often chose to do so if their disease relapses or is considered refractory. Lymphoma research continually evolves as doctors and scientists discover new therapies and more effective ways of giving existing treatments. Chapter 10 describes some of the options currently under investigation. What is stem cell transplantation? There are different types of stem cell transplantation, depending on who donates the stem cells. In an autologous stem cell transplant, the patient is the donor. In an allogeneic stem cell transplant, the donor is another person who is genetically similar to the patient typically a brother or sister, but the donor can also be an unrelated person. The purpose of autologous or full-intensity allogeneic stem cell transplantation is to allow patients to receive high-dose chemotherapy. Such high doses effectively kill cancer cells but also severely damage the bone marrow as a side effect, destroying the body s source of blood cells responsible for fighting infection, preventing bleeding, and carrying oxygen. A stem cell transplantation re-populates the stem cells responsible for making these blood cells. Because high-dose therapy and stem cell transplantation place great strain on a patient s body, they are not options for everyone. In deciding if transplantation is a good option, doctors will consider 55 Understanding Hodgkin Lymphoma

60 the patient s health status, age, medical history, cancer stage, and response to previous therapy. ALLOGENEIC STEM CELL TRANSPLANTATION Stem cell transplantation using stem cells from a donor who is genetically similar to the patient. 1. Collection Stem cells are collected from the donor s bone marrow or blood. 2. Processing Blood or bone marrow may be processed in the laboratory to purify and concentrate the stem cells. 3. Infusion Stem cells are infused into the patient. Part 2 Donor Patient AUTOLOGOUS STEM CELL TRANSPLANTATION Stem cell transplantation using a patient s own stem cells. 1. Collection Stem cells are collected from the patient s bone marrow or blood. Patient 2. Processing Blood or bone marrow may be processed in the laboratory to purify and concentrate the stem cells. Samples are frozen until needed. 3. Reinfusion Stem cells are thawed and reinfused into the patient. Treatment of Hodgkin Lymphoma 56

61 Reduced-intensity transplantation (also called non-myeloablative or mini-allogeneic transplantation) uses lower doses of chemotherapy and/or radiation prior to allogeneic transplantation. This option is available only for allogeneic transplantation and cannot be used for autologous transplantation. This approach takes advantage of the graft-versus-disease effect, in which the transplanted cells (the graft ) recognize the cancerous cells in the patient s body as foreign and destroy them. Patients receiving reduced-intensity transplants may avoid some of the side effects seen with higher-dose chemotherapy, although they still have increased risks of serious side effects as compared with autologous stem cell transplantation due to the potential for graft-versus-host disease (in which immune cells in the transplant recognize the patient cells as foreign and attack them). Questions to Ask Before Deciding to Undergo Stem Cell Transplantation n What type of transplantation is most appropriate for me? PATIENT TIP n Why do you think this is a good idea? n What are the risks associated with this procedure? n Why do you recommend this particular type of transplantation? n If I need a donor, how will I find one? n How long will I need to be in the hospital? n What type of special care will I receive? n How sick will this treatment make me? n What will you do to lessen the side effects? n How will we know if the treatment is working? n How and for how long will the treatment affect my normal activities? n What is my chance of making a full recovery? 57 Understanding Hodgkin Lymphoma

62 For more information on transplantation, visit the Be the Match website at Drug costs: What to do if insurance will not pay Many patients today face the problem of how to pay for rising healthcare costs. Cancer organizations like the Lymphoma Research Foundation ( offer limited financial assistance to patients who qualify. Most pharmaceutical/biotechnology companies have patient assistance programs in place that provide drugs for free to qualifying patients. Patients in need of financial assistance should talk with their doctor and social worker about available options and how to enroll in an appropriate program. Before undergoing a medical procedure, patients should check with their insurance carrier to ensure that it is covered. If there is a dispute about coverage, or if coverage is denied, patients should ask their insurance carrier about its appeals process. Contact your state s department of insurance if a claim is denied. Part 2 When should a clinical trial be considered? Clinical trials are appropriate for patients at all stages of disease. The goal of a clinical trial is to improve the treatment outcome and minimize side effects as compared with standard treatment. When treatments studied in clinical trials are successful, they become the new standard treatments. By participating in a clinical trial, patients may or may not get access to the newest therapies but will receive quality care in a very carefully controlled and supportive environment. Participation in a clinical trial is especially important for patients with HL because it is a rare disease, which makes it very hard to find enough patients to enroll in studies, which are critical for improving treatment. If patients are interested in participating in a clinical study, they should ask their doctor if there is an appropriate trial for them and what the potential risks and benefits may be. Treatment of Hodgkin Lymphoma 58

63 Part 3 Side Effects and Living With Cancer Chapter 7: Common Treatment Side Effects Patients with HL may experience various side effects (also called toxicities) caused by their cancer treatment. Fortunately, medications and lifestyle changes can effectively prevent or lessen the severities of most of these side effects. Patients should ask their healthcare team about possible treatment side effects and how to prevent and manage them, and tell their doctor or nurse if they experience any side effects. This chapter explains the causes of these side effects, the types of side effects caused by different treatments, and steps to take to minimize these side effects. Why does chemotherapy cause side effects or toxicities? Chemotherapy causes side effects because of the non-specific way these drugs attack cancer cells. Most chemotherapy drugs are designed to kill cells like cancer cells that divide rapidly (meaning that they are multiplying quickly). Most normal cells in the body do not divide as quickly as cancer cells. However, healthy cells in hair roots, and cells in the mouth, gastrointestinal tract, and the bone marrow do divide rapidly and can be killed or damaged by chemotherapy. Some chemotherapy drugs can also damage heart or lung cells. The type and severity of side effects caused by chemotherapy vary widely depending on the types of drugs that are given and an individual patient s response. The same drug may cause no side effects in one patient, while in others it may cause anything from very mild to very serious side effects. What is the difference between long-term effects and late effects of treatment? Long-term effects of treatment are toxicities that happen during cancer treatment and continue for months or several years. Fatigue, menopausal symptoms, infertility, and lung problems are examples of long-term effects. 59 Understanding Hodgkin Lymphoma

64 Late effects of treatment become apparent only after treatment has ended and may arise many months, years, or even decades after treatment is completed. Cardiovascular problems, osteoporosis, and secondary cancers (such as lung cancer) are examples of late effects. The likelihood of late secondary cancers and cardiovascular toxicities (heart attacks and strokes) is increased with the use of radiation therapy, particularly if it is extensive. For this reason, the use and duration of radiation therapy have been reduced in current treatment regimens compared with the past. What side effects are caused by chemotherapy? Note that side effects vary depending on the type of chemotherapy; additionally, these adverse effects can have causes other than chemotherapy. Some of the most common side effects include: n Changes in taste. Part 3 n Decreased blood cell production. n Increased chance of infections. n Fatigue. n Hair loss. n Loss of appetite. n Mouth sores. n Nausea and vomiting. n Problems with sexual function. n Cognitive problems (trouble concentrating, impaired memory). n Peripheral neuropathy. Side Effects and Living With Cancer 60

65 Changes in taste Some patients will experience a change in the way foods or beverages taste. Familiar foods may taste differently (dysgeusia) or the flavors of foods may not be as strong (hypogeusia). Some patients may also feel that foods have a metallic taste. These side effects are temporary and usually disappear after the end of chemotherapy. Decreased blood cell production The bone marrow constantly produces red blood cells, white blood cells, and platelets. Some types of chemotherapy and immunotherapy temporarily interfere with the ability of the bone marrow to produce enough of 1 or more of these different types of blood cells. This is called myelosuppression. To prevent and control myelosuppression, samples of a patient s blood are tested for: complete blood count (CBC), which measures the number of red blood cells; differential, which measures the amounts of different types of white blood cells; and the number of platelets. These tests are usually done before and sometimes during each chemotherapy cycle. There are 3 main conditions caused by decreased production of blood cells: Anemia n This is caused by a decrease in the number of red blood cells. n Many chemotherapy drugs cause mild or moderate anemia. n Anemia can make people feel very tired and short of breath; if needed, anemia can be treated with drugs or red blood cell transfusions. 61 Understanding Hodgkin Lymphoma

66 Neutropenia Thrombocytopenia n Neutropenia refers to a decrease in neutrophils the primary type of white blood cells that fight infection. n Patients with low neutrophil count are at risk of serious and even life-threatening infections symptoms of infection include fever, chills, and night sweats. n A normal white blood cell count ranges from 4,000-10,000 cells per microliter. Doctors regularly monitor the absolute neutrophil count (ANC), the number of neutrophils in the peripheral blood. Because patients with an ANC below 500 are at high risk for infections, their doctors may decrease the chemotherapy dosage or delay the next treatment in order to keep the ANC above 500. n Some patients require treatment with antibiotics and hospitalization to prevent or treat infections. n To avoid a patient missing a dose of chemotherapy, doctors sometimes prescribe drugs like filgrastim (Neupogen) and pegfilgrastim (Neulasta) to reduce the duration and severity of neutropenia. These drugs can sometimes cause bone pain which can be relieved with nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen. n Thrombocytopenia refers to a decrease in the number of platelets in the blood; platelets help start the clotting process when bleeding occurs. n Patients with low platelet counts may bruise easily; have cuts that bleed for too long or too much; have nose bleeds or bleeding gums; or may bleed from places that have not been injured. n Some patients require a platelet transfusion to stop or prevent bleeding. Part 3 Side Effects and Living With Cancer 62

67 Reducing Your Risk of Serious Infection During Chemotherapy n If you have a fever of F or greater, call your doctor or go to the emergency room. n Ask your doctor what you should do if you have a sore throat, rash, diarrhea, a cough, or redness, swelling, or pain around a wound. PATIENT TIP Fatigue Fatigue is a common side effect of many types of chemotherapy. Fatigue should decrease after patients have completed their lymphoma treatment, but it could take weeks or months until they return to their normal energy levels. Coping With Fatigue PATIENT TIP n Keep a diary to help you keep track of when you have the most energy and which activities make you feel tired or give you energy. Use this information to plan your activities for the times when you have the most energy. n Ask for help. n Exercise if your doctor says it is okay to do so, but do not overdo it. Try simple stretching and range-of-motion exercises or a short walk; these may energize you without tiring you out. Start slowly and build up to the level that is right for you. Ask your doctor, nurse, or physical therapist to help you create a personal exercise plan. n Rest and sleep during therapy are very important, but do not rest more than you need because it may decrease your energy levels. An afternoon nap helps many patients feel less tired for the rest of the day. Other patients cannot sleep at night if they nap during the day. If you have trouble sleeping, talk to your healthcare team to find out why and what you can do about it. 63 Understanding Hodgkin Lymphoma

68 Hair loss For many patients with HL, hair thinning or loss (alopecia) is one of the most distressing side effects of chemotherapy. This thinning or loss of hair can occur anywhere in the body, including the scalp, eyebrows, eyelashes, arms, legs, and pelvis. The amount of hair loss may vary. If hair loss occurs, it often starts 2 or 3 weeks after the first chemotherapy treatment. Remember that hair loss caused by chemotherapy is usually temporary. Hair will probably grow back after the end of chemotherapy treatments. When the hair first grows back, it may have a slightly different texture or color than it had before treatment. Over time, the texture and color often return to normal. Managing Chemotherapy-Induced Hair Loss PATIENT TIP n After washing it, pat your hair dry instead of rubbing it with a towel. n Brush your hair with a soft-bristle brush or a wide-tooth comb. Part 3 n Do not use curlers and hair dryers. n Do not color or perm your hair, or treat it with other chemicals. n Consider using a wig, scarf, turban, soft cotton hat, or head wrap. Some health insurance companies cover the cost of wigs if you have a doctor s prescription. Check your policy to see if it covers this cost. n Use a hat or scarf to protect your scalp when you are out in the sun. Side Effects and Living With Cancer 64

69 Mouth sores Some chemotherapy drugs can make a patient s mouth become red, sore, or irritated this is called mucositis. Some patients undergoing chemotherapy become more susceptible to viral or fungal infections of the mouth and throat. Patients should tell their doctor if they have a sore throat. The doctor will examine the patient s throat and may take a swab to send to the lab to check for infection. Several medications are available to treat different types of infections. To help decrease chances of infection, patients should have a complete dental checkup and cleaning before starting chemotherapy. Preventing and Caring for Mouth Sores n Clean your mouth and teeth. Use a soft-bristle toothbrush, nonabrasive toothpaste, and lip moisturizer. PATIENT TIP n Do not use mouthwashes that contain alcohol. Your doctor or nurse may recommend a mouth rinse. n Do not eat citrus fruits (such as oranges, grapefruit, lemons, or clementines) or drink citrus juices. n Do not eat spicy foods. n Eat soft foods while you are taking chemotherapy to avoid bruising your gums and other soft tissues in your mouth. n Do not floss your teeth if your blood counts are low. 65 Understanding Hodgkin Lymphoma

70 PATIENT TIP Nausea or vomiting Some chemotherapy drugs can cause nausea or vomiting, usually on the day chemotherapy is administered but sometimes 1 or 2 days later. The doctor may prescribe a drug that prevents vomiting (antiemetic) before chemotherapy. Examples of antiemetics include: aprepitant (Emend), ondansetron (Zofran), granisetron (Kytril), metoclopramide (Reglan), prochlorperazine (Compazine), and dolasetron (Anzemet), and a variety of corticosteroids, such as prednisone (Deltasone). In most cases, these antiemetics are able to partially or completely prevent nausea and vomiting. Controlling or Minimizing Nausea and Vomiting n Before chemotherapy, drink a liquid diet, such as broth, consommé, or water. Do not drink milk. n Do not eat foods that are too hot, cold, sweet, or spicy. Part 3 n Eat smaller and more frequent meals instead of fewer large meals each day. n Avoid strong or offensive smells. Get plenty of fresh air. n Take prescribed antiemetics before chemotherapy to prevent nausea. n If you vomit, make sure to avoid becoming dehydrated. Side Effects and Living With Cancer 66

71 Diarrhea Some types of chemotherapy cause diarrhea. While most patients do not experience severe diarrhea, the most important thing to remember is to avoid dehydration, a loss of body fluids. Call your doctor if you have bloody diarrhea or fever with diarrhea. Avoiding Dehydration From Diarrhea or Vomiting n Drink plenty of liquids (8 glasses a day) such as water or electrolyte replacement drinks like Gatorade and Powerade. n Look for the following signs of dehydration: dry mouth or skin, decreased urine, or feeling dizzy or lightheaded when you stand up. PATIENT TIP n Do not drink or eat milk products because they worsen diarrhea. n Do not eat high fiber and other hard to digest foods because they can worsen diarrhea. n Eat plenty of bananas and other high-potassium food (check with your doctor or dietitian to make sure that these foods will not interfere with your chemotherapy or other medications that you are taking). n Take the medicines that your doctor recommends to control diarrhea or vomiting (call your doctor if symptoms persist). Problems with sexual function Chemotherapy can cause a drop in the sex drive (libido). Usually, a normal libido returns after treatment is finished. Patients should not be embarrassed to talk with their doctor about any problems or concerns they have about changes in their libido. 67 Understanding Hodgkin Lymphoma

72 Sterility Since chemotherapy and radiation may damage sperm and egg cells, it can sometimes cause temporary or permanent sterility, or the inability to have children, in both men and women. The potential for developing sterility depends on the treatment type and specific dose, the number of therapies given, and the patient s age at the time of treatment. Patients should speak with their doctor about fertility preservation (such as treatments to protect the ovaries or cryopreservation of sperm cells, egg cells, or in vitro-fertilized embryos) before starting treatment. For more information and resources about sterility, visit the website for Fertile Hope at Cognitive problems Chemotherapy can result in mild cognitive impairment such as trouble concentrating, impaired memory, or issues with motor control. While such symptoms can be distressful, they typically disappear over time. Part 3 Peripheral neuropathy Some chemotherapy drugs may also cause damage to the nervous system called peripheral neuropathy. Nerve damage can cause side effects such as constipation or a tingling sensation in the fingers and toes. Cardiotoxicity Cardiotoxicity refers to damage to cells in the heart or heart muscle. Long-term use of certain chemotherapy drugs can cause heart damage in some patients. Doxorubicin is an example of a drug that is possibly cardiotoxic. A person s history of heart disease, high cholesterol and high blood pressure, and obesity and lifestyle choices such as smoking and lack of exercise may increase their chance of developing chemotherapyrelated or radiation-related cardiotoxicity. Side Effects and Living With Cancer 68

73 Careful monitoring by the patient s healthcare team can reduce the chances of developing cardiotoxicity. Before deciding to treat patients with a cardiotoxic drug, most doctors will prescribe either an echocardiogram or a MUGA (multi-gated acquisition) scan to measure their cardiac function. This will ensure that the chemotherapy dose is well within the range considered safe for the heart. Lung toxicity Damage to the lungs is a serious side effect that can be caused by bleomycin-containing chemotherapy regimens. Patients should report any changes in lung function such as cough, chest pain, or shortness of breath to their doctor, who may decide to monitor their lung health by regularly performing pulmonary function studies during the course of chemotherapy. Other possible side effects Chemotherapy can also cause other side effects such as cough, skin rashes, general weakness, sore throat, and loss of balance or coordination. Patients are sometimes at increased risk for viral infections, particularly shingles (herpes zoster). Many of these side effects are temporary, but some could last for an extended period. Patients should call their doctor if they experience any painful local rash with or without blisters. What side effects are caused by radiation therapy? Radiation therapy itself is painless, but it can cause short-term and long-term side effects. The side effects caused by radiation therapy vary depending on the type of radiation, the radiation dose, and the part of the body treated. Side effects are usually worse when radiation therapy and chemotherapy are given at the same time. 69 Understanding Hodgkin Lymphoma

74 Examples of Potential Short-Term Side Effects of Radiation Therapy n Radiation to the stomach area can cause nausea, vomiting, and diarrhea. n Radiation to the chest and neck can cause a dry sore throat, mouth sores, and trouble swallowing. n Radiation to any area may cause hair loss in the area and the skin may become red, dry, and tender. n Radiation to the pelvis, legs, and torso (the large areas of your body that contain most of your blood-producing bone marrow) can decrease levels of red blood cells and white blood cells. n Radiation to any part of the body may cause fatigue, which may progressively worsen during the later weeks of the treatment cycle. Part 3 Examples of Potential Long-Term Side Effects of Radiation Therapy n The development of new cancers in the radiated parts of the body. n Cardiovascular damage causing an increased risk of heart attack and stroke. n Lung damage and problems breathing due to radiation to the chest. n Thyroid problems (such as fatigue and weight) later in life due to radiation to the neck. n Headaches, memory loss, personality changes, and trouble concentrating due to radiation to the brain. n Neck muscle weakness ( neck drop ) causing difficulty lifting the head, and neck pain or discomfort. Side Effects and Living With Cancer 70

75 Dry mouth Some patients treated with radiation therapy experience a temporary decrease in saliva production, or dry mouth (xerostomia). People with dry mouth may have problems swallowing foods or thick liquids. Dry mouth can also cause food particles to stick to the teeth and gums. Because saliva helps prevent cavities, doctors may advise patients to go to the dentist for fluoride treatments before they start radiation therapy. Fatigue The likelihood that patients will experience fatigue depends on their disease and the specific radiation plan. Loss of appetite and taste During radiation treatment, patients might lose their appetite for foods that they normally like. The loss of appetite and taste are usually short-term problems. Patients should remember to eat well because their body needs energy and good nutrition to heal. Eating 4 or 5 small meals a day may be more comfortable than eating 2 or 3 larger ones. Patients should ask their healthcare team for information on how to maintain good nutrition during treatment. Nausea Radiation treatment can cause nausea, especially in patients who have radiation to the abdomen. Not eating (especially sweet, spicy, or fatty foods) a few hours before radiation therapy may help avoid nausea. A patient s doctor may prescribe an anti-nausea (antiemetic) medication to be taken before each radiation therapy session. Secondary cancers The risk of developing secondary cancers from radiation therapy depends on factors such as the amount of radiation given (i.e., the dose) and the part of the body treated (i.e., the field). For example, patients with HL treated for limited disease in the chest are at an increased risk for developing breast, lung, or thyroid cancer. Patients with extensive disease in lymph node groups below the diaphragm 71 Understanding Hodgkin Lymphoma

76 are at an increased risk of developing colon cancer and other gastrointestinal cancers. Less common secondary cancers include basal cell skin cancer and sarcomas of the bone and soft tissue. All the data currently available are from when higher doses and larger fields were used. Current contemporary radiation therapy uses significantly modified fields and the exact risk of secondary cancers is unknown. Most secondary malignancies develop more than 10 years after completion of treatment and the risk is highest when radiation therapy is used as part of first-line treatment. Lung cancer and breast cancer are the most common secondary cancers in patients with HL. Recommendations include: n Annual chest x-ray or chest CT for patients at increased risk for lung cancer due to chest radiation therapy, alkylating agent therapy, or smoking history. Part 3 n Annual breast screening by mammography and/or magnetic resonance imaging (MRI) to start no later than 8-10 years after the end of therapy or at age 40 (whichever is earliest) for women who received radiation therapy to the chest or armpit (axilla); these women should also perform monthly self-breast examination and undergo yearly breast examination by a healthcare professional. Cardiovascular damage Radiation therapy can cause damage to the arteries, most commonly those in the neck (carotid arteries) and in the heart (coronary arteries). This increases the risk of stroke and heart attack. Like secondary cancers, this complication increases after 10 years following neck or chest radiation therapy. Screening stress coronary artery tests such as a stress echocardiogram and ultrasound studies of the carotid arteries are often recommended for patients treated with radiation therapy to the neck and/or chest over 10 years previously. Side Effects and Living With Cancer 72

77 Skin reactions Radiation therapy can cause skin changes to the affected area such as redness, itchiness, dry and peeling skin, sores or ulcers, swelling, and puffiness. These skin changes usually decrease and disappear over a few weeks after the radiation therapy ends. Moist areas, such as around the mouth, may be more prone to irritation; the doctor may recommend zinc oxide ointment for these areas. The patient s skin could look and feel as if it was sunburned, and it may eventually peel. Skin Care During and After Radiation Therapy n Be gentle with your skin; do not rub, scrub, or scratch. PATIENT TIP n Use lotions and other skin products that your doctor prescribes or your nurse suggests. n Do not put anything on your skin that is very hot or cold (such as heating pads or ice packs). n Take a shower or bathe in lukewarm water; if you bathe, do it every other day and soak for less than 30 minutes; always use a mild unscented soap; pat dry your skin; do not wash off the ink markings needed for radiation therapy. n Check with your doctor or nurse before using bubble bath, cornstarch, cream, deodorant, hair removers, makeup, oil, ointment, perfume, powder, and sunscreen. n Wear soft clothes and use soft sheets, such as those made with cotton. n Do not wear clothes that are tight and do not allow your skin to breathe. n Make your rooms more humid by placing a bowl of water on the radiator or using a properly cleaned and maintained humidifier. n Do not sunbathe; protect your skin from the sun every day (use a broad-rimmed hat, long-sleeved shirt, and long pants or skirt outside). 73 Understanding Hodgkin Lymphoma

78 n Do not use tanning beds. n Do not put adhesive tape or bandages on your skin. Ask your nurse about ways to bandage without tape. n Ask your doctor or nurse if it is okay to shave the affected area; shave with an electric razor and do not use pre-shave lotion. n Report to your doctor or nurse any skin changes you notice. Throat irritation Radiation therapy to the neck, throat, or chest may cause sore throat, dry mouth, nausea, or cough. Patients may have difficulty eating or swallowing, especially toward the end of their treatment regimen. Patients should tell their doctor if they have problems swallowing. There are treatments for the discomfort. Difficulty swallowing will usually go away after a few weeks of treatment. Part 3 Easing Throat Irritation During Radiation Therapy n Eat bland foods that are soft, smooth, and easy to digest, such as pudding, yogurt, milk shakes, and commercial dietary supplements. PATIENT TIP n Take small bites and swallow each bite completely before taking another. n Try drinking thicker liquids, such as fruit that has been pureed in a blender; they are easier to swallow than thin liquids. n Avoid citrus fruits, especially juices. Side Effects and Living With Cancer 74

79 What side effects are caused by steroids? Cortisone, dexamethasone, prednisone, and other corticosteroid drugs can cause side effects such as insomnia (the inability to fall asleep), increased appetite, mood or personality changes, high blood pressure, and weight gain. Prednisone can also trigger diabetes in patients prone to that disease or make diabetes worse in patients who already have the disease. High doses of steroids can also cause osteoporosis in at-risk patients. Patients should tell their family and friends that personality changes may occur during treatment. Patients should avoid making hasty decisions. If personality changes occur, the doctor should be informed the dose may need to be reduced. What side effects are caused by stem cell transplantation? Patients treated with high doses of chemotherapy and/or radiation before undergoing a stem cell transplant are at increased risk for developing infection, bleeding, and other side effects as described previously (see, What side effects are caused by chemotherapy? and What side effects are caused by radiation therapy? ). Patients receiving high-dose chemotherapy with autologous stem cell support (autologous stem cell transplantation) are followed carefully for the first 3-4 weeks because of the risks of mouth sores (mucositis), infection, anemia (low red blood cell count causing fatigue), and bleeding. Transfusions and antibiotics, often in the hospital, may be necessary. Patients receiving stem cells from a sibling or unrelated donor are also at risk of developing graft-versus-host disease (GVHD), a condition where the donated marrow s immune system attacks the patient s tissues. GVHD can happen at any time after the transplant. Drugs can be used to reduce the risk of developing GVHD or to treat the problem once it develops. 75 Understanding Hodgkin Lymphoma

80 More information about stem cell transplantation and its effects can be found at When should a patient s doctor be called? As a general rule: n Call if the patient experiences a side effect that is unexpected or lasts longer than expected. n Call if the patient experiences a medical problem such as high fever, shortness of breath, prolonged or constant nausea and vomiting, chest pains, and dizziness that cannot wait for a regularly scheduled appointment. n If the patient s doctor or nurse cannot be reached, go to the hospital emergency room for a medical assessment and place another call to the doctor. Part 3 Side Effects and Living With Cancer 76

81 Part 3 Side Effects and Living With Cancer Chapter 8: Managing Your Life During and After Treatment This chapter talks about some general issues that patients may encounter while they live their life during and after treatment. Coping strategies Each person s experience with cancer is different, and how he or she copes with the physical and emotional impact of having HL is unique to a patient s personality and situation. Here are some suggestions for how to cope with some issues that patients may face. Maintain a Strong Support System Get Help for Depression Deal with Physical Changes Maintain a Healthy Lifestyle Communicate your fears and concerns about your disease by talking with your family, friends, doctors, and counselors. Writing down your concerns in a journal may also help. Find a support group or other individuals who are also coping with cancer. Feeling sad or depressed is not unusual in people living with cancer. Watch out for signs of depression: sleeping more or less than usual; feeling a lack of energy; crying; inability to concentrate. Ask for a referral to a psychiatrist, social worker, psychologist, or counselor who will help you cope with your feelings through talk therapy, medications, or both. Find a support group of people who have had similar experiences. Some patients with cancer feel unattractive because of hair loss and other changes in appearance caused by their treatment. Ask your doctor what changes you should expect; plan ahead and buy a wig or head covering if hair loss is a possibility. Get advice from a beautician about makeup for the areas that you consider a problem. Ask your healthcare team for advice on how to manage temporary changes such as dry skin, brittle nails, and a blotchy complexion. Eat a healthy diet that includes fruits, vegetables, protein, and whole grain. Engage in regular physical exercise; this can reduce anxiety, depression, and fatigue, and improve mood. Get sufficient rest to help combat the stress and fatigue of your disease and its treatment. Quit smoking and reduce alcohol consumption. Set Reasonable Goals Having goals for how you want to live your life during and after treatment will help you maintain a sense of purpose. Avoid setting unreasonable goals, such as deciding to work full-time while part-time would be much better for your health. Stay as active and involved as you can in work and other activities that interest you. 77 Understanding Hodgkin Lymphoma

82 The importance of pain control Patients may feel pain from the cancer itself or from treatments and procedures. Cancer pain is very treatable and there is no reason for a patient to tough it out without help. Patients should tell their doctors and nurses if they have any pain because doctors and nurses can offer advice regarding medications and other ways to relieve the pain. Different types of pain are best controlled by different types of pain relievers: n Mild to moderate pain can be treated with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen. n Moderate to severe pain is best controlled with opioids such as morphine, hydromorphone, oxycodone, and hydrocodone. n Tingling and burning pain can be controlled with anti-depressants and anti-epileptics. n Pain caused by swelling can be controlled by steroids such as prednisone and dexamethasone. n Non-drug pain treatments include: biofeedback, breathing and relaxation exercises, distraction, heat or cold packs (avoid these following radiation therapy), hypnosis, imagery, massage, pressure and vibration, and transcutaneous electrical nerve stimulation (TENS). n If the pain is not relieved by medicines and non-drug pain management, the following treatments can also be used to relieve the source of the pain: radiation therapy, nerve blocks/implanted pump, neurosurgery, and surgery. Part 3 Side Effects and Living With Cancer 78

83 Managing Pain PATIENT TIP n Tell your doctor or nurse about your pain. Be specific when you describe it. Where do you feel the pain? What type of pain is it (sharp, dull, throbbing)? Does it come and go, or is it steady? How strong is it? How long does it last? Does anything make the pain feel better or worse? Which drugs have you taken for the pain? Do they help? If so, for how long? n Take your pain medication on a regular schedule even if the pain seems to be better. Do not skip doses. n Tell your family and friends about your pain so that they can help you and so that they can understand why you may be acting differently. n Try deep breathing, yoga, or other ways to relax. n Ask to meet with a pain specialist or palliative care specialist to help you find better ways to control your pain. n Tell your doctor or nurse of any changes in your pain. Maintain a healthy lifestyle Regular physical activity helps keep the cardiovascular system strong and body muscles flexible. Exercise can also help alleviate breathing problems, constipation, and mild depression. It also helps reduce stress and fatigue. Patients should talk to their doctor before starting an exercise program. 79 Understanding Hodgkin Lymphoma

84 Several types of exercise are particularly helpful: n General physical activity, such as swimming, dancing, household chores, and yard work. n Aerobic activity to improve cardiovascular fitness, such as walking, jogging, and bicycling. n Resistance training to strengthen muscles, protect joints, and help remedy osteoporosis by building bone mass. n Flexibility exercises such as stretching and yoga, to improve range of motion, balance, and stability. Eating a healthy diet is especially important during treatment for HL because it will help patients keep up their strength and energy, tolerate treatment-related side effects, decrease their risk of infection, and heal and recover more quickly. Patients should aim for a diet high in fruits and vegetables, protein (poultry, fish, and eggs), and whole grains. During chemotherapy and after a stem cell transplant, a patient may temporarily be asked to avoid raw fruits and vegetables that may increase the risk of infection if you have a low white blood cell count ( neutropenic diet ). A patient s healthcare team can help put together an eating plan that is appropriate. Patients should talk to their doctor before taking any dietary supplements such as multivitamins or individual vitamin supplements, as well as any herbal or natural supplements, because they may interfere with treatments or have unexpected side effects. Part 3 The importance of follow-up care At the first visit following the completion of treatment, patients should talk to their doctor about their follow-up schedule. This will be different from patient to patient depending on their disease type, age, and general health. Patients should adhere to their schedule of follow-up visits these are very important for monitoring disease recurrence and detecting and treating any health problems that might have been caused by the treatment. Side Effects and Living With Cancer 80

85 During these follow-up visits, the doctor will ask about any medical changes since the last appointment and give a physical examination; the doctor may also prescribe imaging, blood, molecular diagnostic, or other laboratory tests. Be proactive in healthcare decisions To stay proactive in healthcare decisions, patients should get the following information from their medical team: n Copies of their medical records and a written summary of their treatment in case they switch oncologists or need to see a primary care physician for routine medical care. n A list of signs of disease recurrence and late side effects from treatment. At the follow-up care appointments, patients should be sure to tell their doctor about: n Any new symptoms. n Pain. n Physical problems that disrupt their daily life such as fatigue, insomnia, sexual dysfunction, and weight gain or loss. n Any new health problems, such as heart disease, diabetes, and high blood pressure. n Any new medications and vitamins they are taking. n Emotional problems such as anxiety and depression. n Any other questions or concerns. 81 Understanding Hodgkin Lymphoma

86 Part 4 Clinical Trials and Advances in Treatment Chapter 9: Overview of Clinical Trials There are hundreds of HL clinical trials now underway in hospitals, cancer centers, and doctors offices around the country. The government, pharmaceutical and biotechnology companies, universities, and doctor groups often sponsor clinical trials. The United States Food and Drug Administration (FDA) and the institutional review board (IRB) of participating hospitals or institutions must approve all clinical trials. What is a clinical trial? A clinical trial is a carefully designed research study that involves people who volunteer to participate. The purpose of clinical trials in cancer is to answer questions about new ways to treat, diagnose, prevent, or manage the disease or the side effects caused by treatments. Strict rules and oversight procedures make sure that clinical trials are designed and run in a way that protects the rights and safety of the people who volunteer to participate. Part 4 In the United States, a new drug must pass through a strict approval process governed by the FDA before it can become a standard therapy for use in people. The FDA-regulated approval process for drugs includes preclinical studies (done in laboratories) and clinical trials (done in hospitals and clinics). As shown in the following table, there are 4 main types (or phases) of clinical trials. The first 3 are usually required before a drug is considered for approval by the FDA. Phase IV studies are performed after a drug has received FDA approval; these trials are sometimes called post-marketing studies. Patients may be eligible to take part in different types of clinical trials depending on their health status, type and stage of lymphoma, and type of treatment, if any, they previously received. Clinical Trials and Advances in Treatment 82

87 Phase Description Number of Volunteer Patients Phase I n To find a safe dose. n people with one or more different types of n To decide on a treatment cancer. regimen. n To see if the treatment causes any side effects. Phase II Phase III Phase IV n To find out if a new treatment has an effect against a certain type of cancer. n To see if the treatment causes any side effects. n To compare new treatments or new uses of existing treatments with current standard treatments. n The main things being compared usually are how well the treatment works and what type of side effects it causes. n To get more information about the long-term safety and effectiveness of a new treatment. n Usually fewer than 100 people with the same type of cancer. n From 100 to several thousand people with the same type of cancer. n Patients are randomly assigned to a treatment group; one group receives the standard therapy and the other group receives the experimental treatment. n Several hundred to several thousand people with the same type of cancer. Why is a placebo sometimes used in phase III trials? A placebo is an inactive ingredient that is used as a comparator in some clinical trials. In such trials neither the patients nor the doctors and nurses treating them will know which patients receive a placebo versus the experimental treatment. In cancer clinical trials, patients are never given a placebo in place of an effective standard therapy. They would be given a placebo only if there were no standard therapies to compare against. Placebo-controlled trials are never done in a manner to deny patients an effective therapy. 83 Understanding Hodgkin Lymphoma

88 Should I participate in a clinical trial? Clinical trials are not a last resort for patients. Patients with all stages of HL can often benefit from participation in clinical trials, whether at the time of initial diagnosis or at relapse. Clinical trials offer patients therapies that are not otherwise available to all patients. Another advantage of clinical trials is that the health of enrolled patients is monitored very carefully. In many cases, patients can benefit more from participation in clinical trials than from receiving standard therapies. Some professional organizations, like the National Comprehensive Cancer Network ( actively encourage the participation of patients with cancer in clinical trials because they provide the best management for any cancer patient. What is informed consent? Informed consent is a process through which people learn all about the clinical trials they are interested in joining. During this process, members of the clinical trial research team will explain: n The purpose of the study. n The factors used to decide if a patient is allowed to participate in the study. n The tests, procedures, and visits participants will be expected to agree to. n The type of treatment provided in the study. Part 4 n The possible risks and benefits. n The rights of patients to decide whether or not to participate, and to leave the study at any time. The research team will answer questions and provide written information about the trial. If patients agree to participate in a clinical trial, they will be asked to read and sign an informed consent form that details all the trial information discussed and describes how their records will be kept private. Clinical Trials and Advances in Treatment 84

89 Remember that even after signing the consent form, patients can leave the study at any time. Questions to Ask About a Clinical Trial n What is the purpose of this clinical trial? PATIENT TIP n Why are you recommending this clinical trial for me? n Who is sponsoring this trial (the National Cancer Institute, a cancer center, a pharmaceutical/biotechnology company)? n Who has reviewed and approved this clinical trial? n Does this clinical trial include the use of a placebo (sugar pill)? n How long will the study last? Where will it take place? n What are the risks involved? n What are the possible benefits? n What are my responsibilities during the clinical trial? n What kinds of tests, procedures, or treatments will be performed? How many and how often? n Will I be in any discomfort or pain? n Will I be able to see my own doctor during the clinical trial? n What costs will I be responsible for? n What happens if my health gets worse during the clinical trial? What is the cost of participating in a clinical trial? Clinical trials are very expensive undertakings for the study sponsor. Patient costs vary depending on the study, who is sponsoring the trial, what portion of the trial-related expenses the sponsor will cover, and the patient s health insurance coverage. Some health insurance and managed healthcare providers will pay for the basic medical procedures associated with the trial, such as lab tests, scans, and hospitalization when required, while others may define clinical trials as experimental or investigational and not cover some of the routine 85 Understanding Hodgkin Lymphoma

90 costs, such as doctor visits, tests, or treatments. Medicare provides coverage for patient care associated with government-sponsored clinical trials. If a patient is taking part in a National Cancer Institute (NCI) trial being conducted at the National Institutes of Health (NIH) in Bethesda, Maryland, the NCI will pay for the study drug and the costs related to the study. A stipend for travel, food, and lodging is also provided. Some cancer centers provide financial assistance or discounted rates for room and board and have special research units that will pay for study-related costs. Some organizations, including the Lymphoma Research Foundation, provide financial assistance for treatmentrelated expenses. Patients should ask their doctor what clinical trials may be most appropriate for them. Here are some additional sources of clinical trial information: n The Lymphoma Helpline at the Lymphoma Research Foundation at (800) n Cancer centers in your area. n The Coalition of Cancer Cooperative Groups website at n The NIH websites and Part 4 Clinical Trials and Advances in Treatment 86

91 Part 4 Clinical Trials and Advances in Treatment Chapter 10: Advances in Treatment of Patients With Hodgkin Lymphoma Over 90% of patients with early-stage classical HL and 80% of those with advanced-stage disease are cured. Because of this high cure rate, minimizing the long-term effects of therapy is a very important issue and a very active area of investigation. Studies are being done to find better ways to identify which patients need aggressive treatment (which carries an increased risk of longterm side effects) and which can be treated with less aggressive therapy, without jeopardizing their chance of being cured. Researchers are also developing treatments that will cause fewer and milder long-term side effects while curing as many patients as possible. Doctors and scientists are also looking for more effective and lesstoxic combination regimens with existing drugs (some of which are in use for other cancers) and with new drugs. New types of drugs being developed include chemotherapy, targeted therapies, and monoclonal antibodies. Drugs that are not yet approved for sale by the FDA are said to be investigational. The most common way for a patient to receive an investigational drug is through a clinical trial. To find out more about getting access to investigational drugs, visit the website for the National Cancer Institute at and search for access to investigational drugs. Chemotherapy Researchers are trying to develop new chemotherapy drugs, make improved versions of existing drugs, and find better ways to combine different doses and sequences of existing drugs. Some drugs being studied in patients with HL are already being used for patients with other cancers. 87 Understanding Hodgkin Lymphoma

92 Monoclonal antibodies and immunoconjugates Monoclonal antibodies are molecules made in the laboratory that are designed to recognize and stick to specific molecules on cancer cells. When a monoclonal antibody attaches itself to a cancer cell, it can stop or slow down its growth or it can make it easier for the immune system to recognize it and kill it. Monoclonal antibodies that target HL-specific molecules are being developed. For example, a phase III study of the monoclonal antibody R-mabHDI is currently planned for patients with lymphocyte predominant HL. Other monoclonal antibodies in phases I and II trials include HeFi-1, apolizumab, and I 131 tositumomab (Bexxar), a monoclonal antibody bound to a radioactive molecule. An immunoconjugate is a monoclonal antibody with a drug attached to it. In 2011, immunoconjugate brentuximab vedotin (Adcetris) became the first new drug approved for the treatment of HL in almost 35 years. Other targeted therapies In addition to monoclonal antibodies that target molecules on cell surfaces, many drugs are in development that target molecules inside cancer cells. A better understanding of the biology and genetics of HL is helping researchers identify specific molecules in lymphoma cells that may be good targets for new drugs. These specific molecules usually have important roles in controlling the growth and survival of lymphoma cells. The drugs that target these molecules are broadly called targeted therapies. These drugs may kill the lymphoma cells or slow down or stop their growth. These targeted therapies attack cancer cells in a more specific way than chemotherapy drugs. Part 4 Many targeted therapies for HL are being studied in laboratory experiments and in clinical trials. For example, the mammalian target of rapamycin (mtor) inhibitors everolimus (Afinitor) and temsirolimus (Torisel) are currently being tested in phase II clinical trials. The histone-deacetylase (HDAC) inhibitors vorinostat, ITF2357, PCI-24781, and MGCD0103 are also being tested in multiple clinical trials. Remember that today s science is moving very fast. Please check with your doctor for additional information and recent updates. Clinical Trials and Advances in Treatment 88

93 ABOUT THE LYMPHOMA RESEARCH FOUNDATION The Lymphoma Research Foundation (LRF) is the nation s largest non-profit organization devoted to funding innovative research and providing people with lymphoma and healthcare professionals with up-to-date information about this type of cancer. LRF s mission is to eradicate lymphoma and serve those touched by this disease. The Foundation remains dedicated to finding a cure for lymphoma through an aggressively-funded research program and by supporting the development of improved therapies for people living with lymphoma. LRF provides a comprehensive series of programs and services for people with lymphoma, their loved ones, and caregivers. How the Lymphoma Research Foundation Serves the Lymphoma Community Research LRF remains dedicated to finding a cure for lymphoma through an aggressively-funded research program. LRF supports innovative research through Clinical Investigator Career Development Awards, Fellowships, and several disease-specific research initiatives. These focused initiatives include: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Initiative; Diffuse Large B-Cell Lymphoma Initiative; Follicular Lymphoma Initiative; and Mantle Cell Lymphoma Initiative and Consortium. The Foundation s volunteer Scientific Advisory Board (SAB), comprised of 45 world-renowned lymphoma experts, guides the Foundation s research activities, seeking out the most innovative and promising lymphoma research projects for support. 89 Understanding Hodgkin Lymphoma

94 Programs and Services LRF provides a comprehensive series of programs and services for the lymphoma community, including: n Clinical Trials Information Service n Disease-Specific Publications and Websites n In-person Workshops and Educational Forums n Lymphoma Helpline n Lymphoma Support Network n Online Resources, Teleconferences, and Webcasts/Podcasts n Patient Aid Grants Professional Education LRF is committed to educating healthcare professionals on the latest developments in lymphoma diagnosis and treatment. The Foundation offers a wide range of lymphoma-focused continuing education activities for nurses, physicians, and social workers, including workshops, conference symposia, and webcasts. Public Policy and Advocacy LRF represents the needs of people with lymphoma by supporting public policies which seek to increase federal funding for lymphoma research and ensure access to high quality cancer care. The LRF Advocacy Program provides volunteer advocates with the resources necessary to garner attention and support for those public policies most important to the lymphoma community. There are currently more than 5,000 LRF advocates in all 50 states and the District of Columbia. About the Lymphoma Research Foundation 90

95 Chapter Network Through its nationwide chapter network, LRF meets the needs of the lymphoma community on the local level. Chapter volunteers reach out to newly diagnosed patients; raise funds for research; and participate in advocacy efforts. There are 18 chapters in 16 states. Contact Information LRF National Headquarters LRF Helpline 115 Broadway, Suite 1301 (800) New York, NY (212) Fax (212) Understanding Hodgkin Lymphoma

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